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Fatty acids in berry lipids of six sea buckthorn (Hippophae rhamnoides L., subspecies carpatica) cultivars grown in Romania | BackgroundA systematic mapping of the phytochemical composition of different sea buckthorn (Hippophae rhamnoides L.) fruit subspecies is still lacking. No data relating to the fatty acid composition of main lipid fractions from the berries of ssp. carpatica (Romania) have been previously reported.ResultsThe fatty acid ... | fatty_acids_in_berry_lipids_of_six_sea_buckthorn_(hippophae_rhamnoides_l.,_subspecies_carpatica)_cul | 3,725 | 271 | 13.745387 | Background<!>Oil content of the SB materials<!><!>Fatty acid composition in oil of pulp/peel, seeds and whole berries<!><!>Fatty acid composition in oil of pulp/peel, seeds and whole berries<!><!>Fatty acid composition in individual lipid fractions of oils from pulp/peel and seeds<!><!>Fatty acid composition of TAGs<!>... | <p>Sea buckthorn (SB) (Hippophae rhamnoides L. Elaeagnaceae) is a bush or a small tree, of the Elaeagnaceae family, naturally distributed in Eurasia. The classification of genus Hippophae is still unclear. The most common species (sp.), H. rhamnoides, was classified in several subspecies (ssp.), including ssp. carpatic... | PubMed Open Access |
Ensemble completeness in conformer sampling: the case of small macrocycles | In this study we compare the three algorithms for the generation of conformer ensembles Biovia BEST, Schrödinger Prime macrocycle sampling (PMM) and Conformator (CONF) form the University of Hamburg, with ensembles derived for exhaustive molecular dynamics simulations applied to a dataset of 7 small macrocycles in two ... | ensemble_completeness_in_conformer_sampling:_the_case_of_small_macrocycles | 8,239 | 242 | 34.045455 | Introduction<!><!>Conformer generation<!>Molecular dynamics simulations<!><!>Processing of dihedral angles<!>Torsion space maps<!>Properties for color-coding of PCA plots<!>Results and discussion<!><!>Results and discussion<!><!>Dependence on charge state<!><!>Dependence on charge state<!>Dependence on solvent<!><!>Dep... | <p>Molecules at ambient conditions are flexible fluctuating three-dimensional objects composed of atoms held together by electrons. Since there exists no appropriate and applicable description for this state, computational chemists apply different types of approximations. For tasks like QSAR/machine learning prediction... | PubMed Open Access |
Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor | The limitation of hydroxamate ester as a chiral Lewis acid coordination moiety was first shown in an intermolecular reaction involving a radical addition and sequential allylation processes. Next, the effect of hydroxamate ester was studied in the cascade addition-cyclization-trapping reaction of substrates with a carb... | cascade_radical_reaction_of_substrates_with_a_carbon–carbon_triple_bond_as_a_radical_acceptor | 1,967 | 93 | 21.150538 | Introduction<!>Results and Discussion<!>Conclusion<!>Supporting Information | <p>Strategies involving a cascade process offer the advantage of multiple carbon-carbon and/or carbon-heteroatom bond formations in a single operation. Radical chemistry has been developed as one of the most powerful tools for carbon-carbon bond formation in organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13]... | Beilstein |
A fingerprint pair analysis of hERG inhibition data | BackgroundDrugs that bind to the human Ether-a-go-go Related Gene (hERG) potassium channel and block its ion conduction can lead to Torsade de Pointes (TdP), a fatal ventricular arrhythmia. Thus, compounds are screened for hERG inhibition in the drug development process; those found to be active face a difficult road t... | a_fingerprint_pair_analysis_of_herg_inhibition_data | 3,122 | 189 | 16.518519 | Background<!><!>Results and discussion<!>Aggregate size distribution vs. mean effect of hERG inhibition<!><!>Aggregate size distribution vs. mean effect of hERG inhibition<!>Size distribution of aggregates follows a power law distribution<!><!>Sets of transformations<!><!>Adding aliphatic oxygen frequently reduces hERG... | <p>Inhibition of the human Ether-a-go-go Related Gene (hERG) channel can be a limiting toxicity for drug candidates. The hERG channel regulates transmembrane movement of potassium ions and is a major contributor to the repolarization phase of the cardiomyocyte action potential in the heart [1]. Inhibition of the hERG c... | PubMed Open Access |
Structures of apo and product-bound human L-asparaginase: Insights into the mechanism of autoproteolysis and substrate hydrolysis | Asparaginases catalyze the hydrolysis of the amino acid asparagine to aspartate and ammonia. Bacterial asparaginases are used in cancer chemotherapy to deplete asparagine from the blood, since several hematological malignancies depend on extracellular asparagine for growth. To avoid the immune response against the bact... | structures_of_apo_and_product-bound_human_l-asparaginase:_insights_into_the_mechanism_of_autoproteol | 5,232 | 241 | 21.709544 | <!>Cloning of human ASNase3<!>Expression and purification of hASNase3<!>Crystallization of hASNase3<!>Data collection and structure solution of hASNase3<!>Cleaved versus uncleaved states of hASNase3<!>Comparison to E. coli Type III asparaginase and hAGA<!>Cleaved and uncleaved ASP-complex structures<!>Product binding t... | <p>Asparaginases are enzymes that catalyze the hydrolysis of the free amino acid asparagine (ASN) into aspartate (ASP) and ammonia. The human genome codes for at least three enzymes that can catalyze this reaction, though the true physiological substrate of these enzymes may not be the free amino acid. One is actually ... | PubMed Author Manuscript |
A CycloRGDf(Me-V) Analog as Chemical Probe to Study Integrins Function in Living Cells | Studying the role of integrins in cellular processes requires the ability to monitor their localization in dynamic events. We report a chemical probe that can be used to image integrins in living cells. The fluorescent probe was derived from cyclo-RGDf(Me-V), a compound selective for integrins that possess an RGD-bindi... | a_cyclorgdf(me-v)_analog_as_chemical_probe_to_study_integrins_function_in_living_cells | 2,878 | 134 | 21.477612 | ■ INTRODUCTION<!>■ RESULTS AND DISCUSSION<!>Labeling Integrins in Cells<!>Imaging Probes Cilengitide-PB405 (2) and Cilengitide-A568 (3) Label Endogenous Integrin αVβ5<!>■ CONCLUSION<!>■ SIGNIFICANCE<!>■ AUTHORS CONTRIBUTIONS | <p>Integrins are heterodimeric transmembrane proteins found at the surface of cells, where they connect the intracellular cytoskeleton to the extracellular matrix. Besides being essential structural elements of cells, they also play important signaling roles in development and in pathology. [1] The function of integrin... | ChemRxiv |
Quantum dynamics study of energy requirement on reactivity for the HBr + OH reaction with a negative-energy barrier | A time-dependent, quantum reaction dynamics approach in full dimensional, six degrees of freedom was carried out to study the energy requirement on reactivity for the HBr + OH reaction with an early, negative energy barrier. The calculation shows both the HBr and OH vibrational excitations enhance the reactivity. Howev... | quantum_dynamics_study_of_energy_requirement_on_reactivity_for_the_hbr_+_oh_reaction_with_a_negative | 3,592 | 622 | 5.77492 | <!>Results and Discussion<!>Rotational excitations ICSs.<!>Discussion<!>Theoretical Methods<!> | <p>hydrogen abstraction reaction HBr + OH over a wide range of temperatures 23-2000 K, by employing the improved canonical variational transition-state theory (VTST) 23 with a small-curvature tunneling correction.</p><p>Recently, Bowman's group 24 has developed a high-quality, full dimensional PES for the HBr + OH syst... | Scientific Reports - Nature |
Theoretical, Solid-State and Solution Quantification of the Hydrogen Bond Enhanced Halogen Bond | Proximal noncovalent forces are commonplace in natural systems and understanding the consequences of their juxtaposition is critical. This paper experimentally quantifies for the first time a Hydrogen Bond enhanced Halogen Bond (HBeXB) without the complexities of protein structure or preorganization. An HBeXB is a halo... | theoretical,_solid-state_and_solution_quantification_of_the_hydrogen_bond_enhanced_halogen_bond | 3,569 | 139 | 25.676259 | Introduction<!>Design considerations<!>Computational evaluations<!>Molecular electrostatic potential analysis<!>Interaction energy analysis<!>Comparison to substituent effects<!>Other Functionals & Complexation Energy<!>Structural evaluations of HBeXB and XB systems<!>Solution evaluation of the HBeXB<!>Conclusion | <p>Electronegative substituents in polar covalent bonds are usually adept hydrogen bond acceptors. However, terminal organohalogens are paradoxical, as they are considered weak hydrogen bond acceptors.[1] Despite decades of hydrogen bond research, the rationale for this observation remains largely enigmatic.[2] Efforts... | PubMed Author Manuscript |
The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives | An extension of the substrate scope of the Flögel-three-component reaction of lithiated alkoxyallenes, nitriles and carboxylic acids is presented. The use of dicarboxylic acids allowed the preparation of symmetrical bis(β-ketoenamides) from simple starting materials in moderate yields. Cyclocondensations of these enami... | the_flögel-three-component_reaction_with_dicarboxylic_acids_–_an_approach_to_bis(β-alkoxy-β-ketoenam | 3,385 | 111 | 30.495495 | <!>Introduction<!><!>Introduction<!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Conclusion<!>General methods<!>Three-component-reaction of m... | <p>This article is part of the Thematic Series "Multicomponent reactions II".</p><!><p>Multicomponent reactions (MCRs) generally allow a diversity-oriented fast and efficient access to complex synthetic intermediates and are thus powerful tools for the assembly of small-molecule libraries [1–2]. MCRs leading to functio... | PubMed Open Access |
The DNA polymerase activity of Pol ε holoenzyme is required for rapid and efficient chromosomal DNA replication in Xenopus egg extracts | BackgroundDNA polymerase ε (Pol ε) is involved in DNA replication, repair, and cell-cycle checkpoint control in eukaryotic cells. Although the roles of replicative Pol α and Pol δ in chromosomal DNA replication are relatively well understood and well documented, the precise role of Pol ε in chromosomal DNA replication ... | the_dna_polymerase_activity_of_pol_ε_holoenzyme_is_required_for_rapid_and_efficient_chromosomal_dna_ | 4,812 | 223 | 21.578475 | Background<!>Isolation of cDNA encoding each subunit of Xenopus Pol ε holoenzyme<!>The C-terminal Zinc finger domain of p260 is required for binding p60 but not p12-p17<!><!>DNA polymerase activity of xPol ε holoenzyme is required for DNA synthesis in Xenopus egg extracts<!><!>DNA polymerase activity of xPol ε holoenzy... | <p>Three structurally and functionally distinct DNA polymerases, known as DNA polymerases α, δ, and ε (Pol α,-δ, and -ε, respectively), are required for chromosomal DNA replication in yeasts [1-3]. The complex structure of each Pol α, -δ, and -ε is well conserved from yeast to human [4], thus their function inside the ... | PubMed Open Access |
Modified Ti-MWW Zeolite as a Highly Efficient Catalyst for the Cyclopentene Epoxidation Reaction | The liquid-phase epoxidation of cyclopentene (CPE) was performed in the Ti-zeolite/H2O2 catalytic system for the clean synthesis of cyclopentene oxide. Among all the Ti-zeolites (Ti-Beta, Ti-MOR, Ti-MCM-68, TS-1, TS-2, and Ti-MWW) investigated in the present study, Ti-MWW provided relatively lower CPE conversion of 13%... | modified_ti-mww_zeolite_as_a_highly_efficient_catalyst_for_the_cyclopentene_epoxidation_reaction | 5,869 | 153 | 38.359477 | Introduction<!>Preparation of Ti-MWW<!>Structural Rearrangement of Ti-MWW<!>Synthesis of Different Titanosilicates<!>Characterization Methods<!>Catalytic Experiments<!>Effect of the Topologies of the Titanosilicates<!><!>Influence of the Nature of Solvents<!><!>Influence of the Nature of Solvents<!>A comparison of the ... | <p>Epoxy compounds, as important organic intermediates and chemical raw materials, can easily undergo ring-opening reactions with water, alcohols, amines, ammonia, or carboxylic acids to form a series of fine and bulk chemicals in the fields of petrochemical industry, polymer synthesis, and pharmaceuticals (Imamura et ... | PubMed Open Access |
In Vivo Manifestation of Notch Related Phenotypes in Zebrafish Treated with Alzheimer\xe2\x80\x99s Amyloid Reducing \xce\xb3-Secretase Inhibitors | \xce\xb3-Secretase is responsible for the final cleavage of amyloid precursor protein to generate the amyloid-\xce\xb2 protein, the major component of plaques in the brains of Alzheimer\xe2\x80\x99s disease patients. \xce\xb3-Secretase inhibitors (GSI) have been explored for therapeutic inhibition of A\xce\xb2 generati... | in_vivo_manifestation_of_notch_related_phenotypes_in_zebrafish_treated_with_alzheimer\xe2\x80\x99s_a | 4,869 | 272 | 17.900735 | INTRODUCTION<!>Embryo Treatment<!>Blocking A\xce\xb2 production by \xce\xb3-secretase inhibitors<!>In Vitro \xce\xb3-Secretase Activity Assay<!>Conventional Microscope Imaging<!>In situ Hybridization<!>Heart rate, pigmentation and swim bladder Analysis<!>Inhibition of \xce\xb3-secretase activity in cultured cells treat... | <p>Alzheimer's disease (AD) is pathologically characterized by the presence of extracellular neuritic plaques and intracellular neurofibrillary tangles (Selkoe 1999). While the neurofibrillary tangles are mainly composed of hyperphosphorylated Tau protein, the neuritic plaques are formed by a gradual accumulation of am... | PubMed Author Manuscript |
The pKa Distribution of Drugs: Application to Drug Discovery | The acid-base dissociation constant (pKa) of a drug is a key physicochemical parameter influencing many biopharmaceutical characteristics. While this has been well established, the overall proportion of non-ionizable and ionizable compounds for drug-like substances is not well known. Even less well known is the overall... | the_pka_distribution_of_drugs:_application_to_drug_discovery | 5,956 | 345 | 17.263768 | Introduction<!>Drug-likeness<!>pKa data sources and analysis<!>Methods<!>(a) Acid and base proportions<!>(b) pKa Distribution of single acid containing compounds<!>(c) pKa Distribution of single base containing compounds<!>(d) pKa Distribution of simple ampholytes<!>Overview of findings<!>Application of findings<!>Pers... | <p>An awareness of the influence of the acid-base dissociation constant, pKa, on the biopharmaceutical properties of drugs and chemicals has long been established within the pharmaceutical and chemical industry. As the majority of drugs are weak acids and/or bases, knowledge of the dissociation constant in each case he... | PubMed Open Access |
Haloboration: scope, mechanism and utility | Haloboration, the addition of B–X (X = Cl, Br, I) across an unsaturated moiety e.g., C <svg xmlns="http://www.w3.org/2000/svg" version="1.0" width="13.200000pt" height="16.000000pt" viewBox="0 0 13.200000 16.000000" preserveAspectRatio="xMidYMid meet"><metadata> Created by potrace 1.16, written by Peter Selinger 2001-2... | haloboration:_scope,_mechanism_and_utility | 5,913 | 274 | 21.580292 | Introduction<!>The early work<!>Mechanistic studies<!>Recent studies into the bromoboration of simple alkynes with BBr3<!>1,1-Bromoboration of internal alkynes<!>Other alkyne haloboration reactions<!>Borocation mediated chloroboration of alkynes<!>1,2-trans-Chloroboration of alkynes<!>1,3-Chloroboration of alkynes<!>Ch... | <p>Since the end of the last millennium, the principle of sustainability and atom economy increasingly has impacted the way scientific research is done.1 A chemical transformation that is 100% atom efficient is the addition reaction, in which a reagent is added across a multiple bond (e.g., CC, CC, or CE, E: O, NR). On... | PubMed Open Access |
2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists | A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher a... | 2-sulfonamidopyridine_c-region_analogs_of_2-(3-fluoro-4-methylsulfonamidophenyl)propanamides_as_pote | 6,585 | 82 | 80.304878 | Introduction<!>Chemistry<!>Biological activity<!>Molecular modeling<!>Conclusion<!>General<!>Method A:<!>Method B:<!>2-(4-Methoxybenzyl)amino-6-(trifluoromethyl)nicotinonitrile (R1 = (4-OMe)Bn).<!>2-Methylamino-6-(trifluoromethyl)nicotinonitrile (R1 = Me).<!>2-Isopropylamino-6-(trifluoromethyl)nicotinonitrile (R1 = i-P... | <p>TRPV1 has emerged as an exciting therapeutic target for chronic and inflammatory pain as well as for the numerous other conditions in which C-fiber sensory afferent neurons are involved.1–3 The natural products capsaicin4 and resiniferatoxin5 provided critical initial lead structures guiding the current vigorous eff... | PubMed Author Manuscript |
Evolving Stark Effect During Growth of Perovskite Nanocrystals Measured Using Transient Absorption | Methylammonium lead triiodide (MAPbI3) nanocrystals (NCs) are emerging materials for a range of optoelectronic applications. Photophysical characterization is typically limited to structurally stable NCs owing to the long timescales required for many spectroscopies, preventing the accurate measurement of NCs during gro... | evolving_stark_effect_during_growth_of_perovskite_nanocrystals_measured_using_transient_absorption | 3,878 | 174 | 22.287356 | 1. Introduction<!><!>1. Introduction<!><!>2.1. Materials<!>2.2. Nanocrystal Synthesis<!>2.3. Absorbance and Fluoresence<!>2.4. Single-Shot Transient Absorption<!>3. Results and Discussion<!><!>3. Results and Discussion<!><!>3. Results and Discussion<!><!>3. Results and Discussion<!><!>3. Results and Discussion<!><!>3. ... | <p>Hybrid organic-inorganic perovskite nanocrystals (NCs) are currently the focus of significant interest owing to their potential applications in optoelectronic devices. Their large absorption coefficients (Fu et al., 2015), high defect tolerance (Dirin et al., 2016), excellent photoluminescence quantum yield (PLQY) (... | PubMed Open Access |
Restricted Photochemistry in the Molecular Solid State: Structural changes on Photoexcitation of Cu(I) Phenanthroline metal-to-ligand-charge-transfer (MLCT) complexes by Time-Resolved Diffraction | The excited state structure of [Cu(1)[(1,10-phenanthroline-N,N\xe2\x80\x99) bis(triphenylphosphine)] cations in their crystalline [BF4] salt has been determined at both 180 and 90K by single-pulse time-resolved synchrotron experiments with the modified polychromatic Laue method. The two independent molecules in the cry... | restricted_photochemistry_in_the_molecular_solid_state:_structural_changes_on_photoexcitation_of_cu( | 3,076 | 205 | 15.004878 | 1. Introduction<!>2.1 Data collection<!>2.2 Data processing<!>2.3 Collection of monochromatic data<!>2.4 Measurement of emission lifetimes at different temperatures<!>2.5 Theoretical calculations<!>3.1 Photodifference maps<!>3.2 Least-squares refinement<!>3.3 Analysis of temperature differences due to laser exposure<!>... | <p>Electron injection from molecular sensitizers absorbed on semiconductor surfaces to the underlying substrate have become an increasingly important subject due to their relevance for the mode of operation of photovoltaic cells. The precise geometry of the binding modes of the sensitizers to the underlying substrate h... | PubMed Author Manuscript |
Using informative features in machine learning based method for COVID-19 drug repurposing | Coronavirus disease 2019 (COVID-19) is caused by a novel virus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This virus induced a large number of deaths and millions of confirmed cases worldwide, creating a serious danger to public health. However, there are no specific therapies or drugs availabl... | using_informative_features_in_machine_learning_based_method_for_covid-19_drug_repurposing | 5,307 | 203 | 26.142857 | Introduction<!>Finding essential proteins related to COVID-19 pathology as candidate drug targets<!>Construction of COVID-19 related biological network<!>Disruption of COVID-19 related biological processes<!>Algorithm 1: spectral partitioning<!>Algorithm 2: betweenness value<!>Candidate essential proteins associated wi... | <p>The pandemic situation for Coronavirus disease 2019 (COVID-19) causes more than 197 million infections and more than 4.2 million deaths in more than 200 countries worldwide (until the end of July 2021) and this number is increasing rapidly. Due to this rapid spread, researchers have been searching for therapeutic ap... | PubMed Open Access |
A Crowding Barrier to Protein Inhibition in Colloidal Aggregates | Small molecule colloidal aggregates adsorb and partially denature proteins, inhibiting them artifactually. Oddly, this inhibition is typically time-dependent. Two mechanisms might explain this: low concentrations of the colloid and enzyme might mean low encounter rates, or colloid-based protein denaturation might impos... | a_crowding_barrier_to_protein_inhibition_in_colloidal_aggregates | 3,608 | 146 | 24.712329 | INTRODUCTION<!>RESULTS<!>DISCUSSION AND CONCLUSIONS<!>Dynamic Light Scattering.<!>Enzyme Inhibition. | <p>Many organic molecules, including drugs, investigational new drugs, clinical candidates,1–4 and especially early leads in drug discovery,5–8 aggregate into densely packed colloids at micromolar or even submicromolar concentrations in bio-chemical buffers.9 These aggregates sequester 105 to 106 protein molecules,10,1... | PubMed Author Manuscript |
Single-molecule photoredox catalysis | The chemistry of life is founded on light, so is it appropriate to think of light as a chemical substance? Planck's quantization offers a metric analogous to Avogadro's number to relate the number of particles to an effective reaction of single molecules and photons to form a new compound. A rhodamine dye molecule serv... | single-molecule_photoredox_catalysis | 3,220 | 157 | 20.509554 | Introduction<!>Single-molecule imaging<!>(a)<!>Single-molecule photon-correlation spectroscopy<!>Discussion<!>Conflicts of interest | <p>Photosynthesis is the archetypal photocatalytic process. Having evolved from primordial life over billions of years, the conversion of sunlight into chemical energy remains enigmatic at once in its elegance and complexity. Whereas nature combines the energy of multiple photons to drive the conversion of carbon dioxi... | Royal Society of Chemistry (RSC) |
Peptide array–based interactomics | The analysis of protein-protein interactions (PPIs) is essential for the understanding of cellular signaling. Besides probing PPIs with immunoprecipitation-based techniques, peptide pull-downs are an alternative tool specifically useful to study interactome changes induced by post-translational modifications. Peptides ... | peptide_array–based_interactomics | 1,805 | 195 | 9.25641 | Introduction<!><!>Immunoprecipitations and peptide pull-downs<!>Peptide pull-down meets mass spectrometry<!>Linear motifs as interaction mediators<!><!>Linear motifs as interaction mediators<!>Peptide array–based interaction screens<!>Outlook<!> | <p>Cellular signaling is in large parts based on a complex network of protein interactions with other proteins or other biological molecules. Studying protein-protein interaction (PPI) networks is pivotal for the understanding of cellular signaling [1–3]. Protein-protein interactions can be studied in different ways, i... | PubMed Open Access |
One-pot multistep mechanochemical synthesis of fluorinated pyrazolones | Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approa... | one-pot_multistep_mechanochemical_synthesis_of_fluorinated_pyrazolones | 1,698 | 90 | 18.866667 | Introduction<!>Results and Discussion<!>Conclusion | <p>Mechanochemical methods are emerging as an alternative approach to traditional solvent-based reactions for chemical synthesis. Under mechanochemical conditions reactions are performed between neat reagents and do not require a solvent. Processing chemical reactions in such a manner is desirable as reactions are cons... | Beilstein |
Multiscale simulations identify origins of differential carbapenem hydrolysis by the OXA-48 β-lactamase | OXA-48 β-lactamases are frequently encountered in bacterial infections caused by carbapenem-resistant Gram-negative bacteria. Due to the importance of carbapenems in treatment of healthcare-associated infections, and the increasingly wide dissemination of OXA-48-like enzymes on plasmids, these βlactamases are of high c... | multiscale_simulations_identify_origins_of_differential_carbapenem_hydrolysis_by_the_oxa-48_β-lactam | 6,630 | 240 | 27.625 | Introduction<!>Methods<!>Results & Discussion<!>Deacylation efficiencies for different orientations of the 6α-hydroxyethyl group<!>Comparison of carbapenem deacylation in orientation I<!>Comparison with experimental data<!>Conclusions | <p>The World Health organization describes antibiotic resistance as "...one of the biggest threats to global health, food security, and development today." 2 Antibiotic resistance arises naturally and evolved long ago, 3 but its emergence and dissemination have been considerably accelerated by the current excessive use... | ChemRxiv |
Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal | SYNOPSIS Mitochondria play a critical role in mediating the cellular response to oxidants formed during acute and chronic cardiac dysfunction. It is widely assumed that, as cells are subject to stress, mitochondria are capable of drawing upon a \xe2\x80\x9creserve capacity\xe2\x80\x9d which is available to serve the in... | importance_of_the_bioenergetic_reserve_capacity_in_response_to_cardiomyocyte_stress_induced_by_4-hyd | 5,168 | 251 | 20.589641 | INTRODUCTION<!>Materials<!>Neonatal rat ventricular myocyte primary cultures<!>Bioenergetic measurements<!>Protein-HNE and GSH measurements<!>Cell death assays<!>Statistical analysis<!>Protein HNE adducts and cell death increase with HNE treatment<!>Effect of HNE on aerobic metabolism in intact neonatal cardiomyocytes<... | <p>Defining the role of mitochondria in various cardiovascular pathologies is currently an area of great interest, with many studies focusing on the properties of the organelle isolated from diseased or stressed cardiac cells. These studies now point to the importance of understanding how changes in isolated mitochondr... | PubMed Author Manuscript |
N7 Methylation Alters Hydrogen Bonding Patterns of Guanine in Duplex DNA | N7-Alkyl-2\xe2\x80\xb2-deoxyguanosines are major adducts in DNA that are generated by various alkylating mutagens and drugs. However, the effect of the N7-alkylation on the hydrogen bonding patterns of the guanine remains poorly understood. We prepared N7-methyl-2\xe2\x80\xb2-deoxyguanosine (N7mdG)-containing DNA using... | n7_methylation_alters_hydrogen_bonding_patterns_of_guanine_in_duplex_dna | 1,685 | 202 | 8.341584 | <p>A large number of alkylating anticancer agents and mutagens such as the nitrogen mustards, azinomycins, leinamycin, styrene oxide and aflatoxin B1 attack the N7 of guanine, the most nucleophilic atom within DNA, to primarily generate N7-alkyl-2′-deoxyguanosines (N7-alkyl-dG).1,2 The positively charged N7-alkyl-dG ha... | PubMed Author Manuscript | |
Discovery of cellular substrates for protein kinase A using a peptide array screening protocol | Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification. Resultant changes in activity, localization or stability of phosphoproteins ... | discovery_of_cellular_substrates_for_protein_kinase_a_using_a_peptide_array_screening_protocol | 3,420 | 222 | 15.405405 | INTRODUCTION<!>Reagents and antibodies<!>Database searching<!>SPOT synthesis<!>Membrane phosphorylation and blotting<!>cDNA cloning<!>Phosphorylation experiments<!>Confocal microscopy<!>Cell growth assays<!>RESULTS AND DISCUSSION | <p>Protein kinases regulate all aspects of cellular behaviour. These key signal transduction enzymes act by phosphorylating target sequences in substrates. This results in modulation of protein function or stability, alterations in association with other proteins, or the movement from one cellular compartment to anothe... | PubMed Author Manuscript |
Synthesis of disulfide-rich heterodimeric peptides through an auxiliary N, N-crosslink | Insulins, relaxins, and other insulin-like peptides present a longstanding synthetic challenge due to their unique cysteine-rich heterodimeric structure. While their three disulfide signature is conserved within the insulin superfamily, sequences of the constituent chains exhibit considerable diversity. As a result, me... | synthesis_of_disulfide-rich_heterodimeric_peptides_through_an_auxiliary_n,_n-crosslink | 2,616 | 146 | 17.917808 | <!>Results<!>Synthesis of relaxin. The synthesis of relaxin (Supplementary Figures<!>Discussion | <p>O ver the course of the last 50 years, the efficiency in linear peptide assembly has advanced through a series of innovations, most notably stepwise solid-phase synthesis and fragment ligation [1][2][3][4] . Still, precise control of higher order structure through directed disulfide bond formation remains challengin... | Nature Communications Chemistry |
Analytical expressions for the homotropic binding of ligand to protein dimers and trimers | Cooperative binding of a ligand to multiple subsites on a protein is a common theme among enzymes and receptors. The analysis of cooperative binding data (either positive or negative) often relies on the assumption that free ligand concentration, L, can be approximated by the total ligand concentration, LT. When this a... | analytical_expressions_for_the_homotropic_binding_of_ligand_to_protein_dimers_and_trimers | 2,786 | 134 | 20.791045 | <!>The models<!>Theory<!>The L \xe2\x89\x88 LT approximation<!>The Excel worksheets<!>Application to spectroscopic methods<!>Conclusions | <p>Protein–ligand interactions are fundamental to numerous biological processes, including hormone signaling, allosteric regulation, metabolism, and cell-to-cell communication. A key metric for such interactions is the dissociation constant (Kd), which is often determined in equilibrium binding titrations where the con... | PubMed Author Manuscript |
Rates of insulin secretion in INS-1 cells are enhanced by coupling to anaplerosis and Kreb\xe2\x80\x99s cycle flux independent of ATP synthesis | Mechanistic models of glucose stimulated insulin secretion (GSIS) established in minimal media in vitro, may not accurately describe the complexity of coupling metabolism with insulin secretion that occurs in vivo. As a first approximation, we have evaluated metabolic pathways in a typical growth media, DMEM as a surro... | rates_of_insulin_secretion_in_ins-1_cells_are_enhanced_by_coupling_to_anaplerosis_and_kreb\xe2\x80\x | 2,655 | 292 | 9.092466 | Introduction<!>Cell culture<!>13C-Isotopomer studies of anaplerotic pathways<!>Metabolite Analysis<!>Oxidative Phosphorylation: 31P-NMR Measured Rates of ATP Synthesis and Fluorometric Measured Rates of Oxygen Consumption<!>Oxygen consumption rates<!>Viability of entrapped cells as determined by OCR<!>Statistical analy... | <p>Mechanistic models of glucose stimulated insulin secretion (GSIS) established in minimal media in vitro, may not accurately describe the complexity of coupling metabolism with insulin secretion that occurs in vivo. Central to the mechanism of nutrient-stimulated insulin secretion is that increases in mitochondrial o... | PubMed Author Manuscript |
Evaluating the Viability of Successive Ring‐Expansions Based on Amino Acid and Hydroxyacid Side‐Chain Insertion | AbstractThe outcome of ring‐expansion reactions based on amino/hydroxyacid side‐chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam an... | evaluating_the_viability_of_successive_ring‐expansions_based_on_amino_acid_and_hydroxyacid_side‐chai | 3,867 | 137 | 28.226277 | <!>Introduction<!><!>Introduction<!><!>Introduction<!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Computational chemistry: Method evaluation<!><!>Computational chemistry: Method evaluation<!><!>Co... | <p>A. Lawer, R. G. Epton, T. C. Stephens, K. Y. Palate, M. Lodi, E. Marotte, K. J. Lamb, J. K. Sangha, J. M. Lynam, W. P. Unsworth, Chem. Eur. J.
2020, 26, 12674.</p><!><p>Rearrangements that allow ring‐enlarged products to be prepared from smaller cyclic systems have much utility in synthetic chemistry.1, 2 Ring expan... | PubMed Open Access |
Ultra-long Magnetic Nanochains for Highly Efficient Arsenic Removal from Water | The contamination of drinking water with naturally occurring arsenic is a global health threat. Filters that are packed with adsorbent media with a high affinity for arsenic have been used to de-contaminate water \xe2\x80\x94 generally iron or aluminium oxides are favored materials. Recently, nanoparticles have been in... | ultra-long_magnetic_nanochains_for_highly_efficient_arsenic_removal_from_water | 3,640 | 178 | 20.449438 | Introduction<!>Chemicals<!>Synthesis of High Surface Area Magnetic Nanochains<!>Characterization<!>Arsenic Adsorption Test<!>Results and Discussion<!>Conclusion | <p>Arsenic-contaminated drinking water is a serious global health concern due to its high toxicity and carcinogenicity.1-5 The contamination in drinking water sources is estimated to affect over 144 million people around the world,6, 7 spurring the development of numerous water treatment technologies to limit negative ... | PubMed Author Manuscript |
Anlotinib combined with temozolomide suppresses glioblastoma growth via mediation of JAK2/STAT3 signaling pathway | PurposeAnlotinib protects against carcinogenesis through the induction of autophagy and apoptosis. The current study evaluated the role and molecular mechanisms of anlotinib in glioblastoma, and the effects of anlotinib in combination with temozolomide (TMZ).MethodsCell Counting Kit-8 and colony-forming assays were use... | anlotinib_combined_with_temozolomide_suppresses_glioblastoma_growth_via_mediation_of_jak2/stat3_sign | 4,046 | 240 | 16.858333 | Introduction<!>Cell culture<!>Reagents and antibodies<!>Cell viability assay<!>Colony-forming assay<!>Wound-healing assay<!>Migration and invasion assay<!>Flow cytometry<!>Western blot<!>ELISA and tubular formation assay<!>Immunofluorescence<!>Xenograft experiments and IHC<!>Statistical analysis<!><!>Anlotinib suppress... | <p>Gliomas are the most common primary intracranial tumor. More than half of all gliomas are malignant in adults, and comprise more than 80% of malignant tumors in the central nervous system. Glioblastoma multiforme (GBM) accounts for more than 50% of total gliomas [1]. The standard treatment option of GBM is surgery a... | PubMed Open Access |
Synthesis and Biological Evaluation of Dantrolene‐Like Hydrazide and Hydrazone Analogues as Multitarget Agents for Neurodegenerative Diseases | AbstractDantrolene, a drug used for the management of malignant hyperthermia, had been recently evaluated for prospective repurposing as multitarget agent for neurodegenerative syndromes, including Alzheimer's disease (AD). Herein, twenty‐one dantrolene‐like hydrazide and hydrazone analogues were synthesized with the a... | synthesis_and_biological_evaluation_of_dantrolene‐like_hydrazide_and_hydrazone_analogues_as_multitar | 5,180 | 165 | 31.393939 | <!>Introduction<!><!>Introduction<!><!>Chemistry<!><!>Inhibition of MAOs and AChE<!><!>Inhibition of MAOs and AChE<!><!>Inhibition of MAOs and AChE<!><!>Inhibition of MAOs and AChE<!>Cell‐based assay of neuroprotection<!><!>Hydrolytic stability in buffered solution<!><!>Activation of carnitine/acylcarnitine carrier (CA... | <p>I. Bolognino, N. Giangregorio, A. Tonazzi, A. L. Martínez, C. D. Altomare, M. I. Loza, S. Sablone, S. Cellamare, M. Catto, ChemMedChem
2021, 16, 2807.</p><!><p>Dantrolene (DAN; Figure 1) is a drug specifically used in the management of malignant hyperthermia, a life‐threatening pathology with fatal course. In a rece... | PubMed Open Access |
Structure of the competence pilus major pilin ComGC in Streptococcus pneumoniae | Type IV pili are important virulence factors on the surface of many pathogenic bacteria and have been implicated in a wide range of diverse functions, including attachment, twitching motility, biofilm formation, and horizontal gene transfer. The respiratory pathogen Streptococcus pneumoniae deploys type IV pili to take... | structure_of_the_competence_pilus_major_pilin_comgc_in_streptococcus_pneumoniae | 6,666 | 197 | 33.837563 | Introduction<!>ComGC is the major pilin in S. pneumoniae competence-induced pili<!><!>ComGC is the major pilin in S. pneumoniae competence-induced pili<!>Structural features of pneumococcal ComGC filaments<!><!>ComGC processing and dimerization in the membrane<!><!>ComGC processing and dimerization in the membrane<!>St... | <p>Type IV pili are important virulence factors on the surface of many pathogenic bacteria. These extracellular appendages can be several microns long and are involved in various functions, including adherence (1, 2), twitching motility (3, 4), biofilm formation (5, 6), and DNA uptake (7–9). Type IV pili are composed o... | PubMed Open Access |
Phosphine Catalysis of Allenes with Electrophiles | Nucleophilic phosphine catalysis of allenes with electrophiles is one of the most powerful and straightforward synthetic strategies for the generation of highly functionalized carbocycle or heterocycle structural motifs, which are present in a wide range of bioactive natural products and medicinally important substance... | phosphine_catalysis_of_allenes_with_electrophiles | 3,967 | 77 | 51.519481 | 1. Introduction<!>2.1. [3+2] Annulation with electron-deficient olefins<!>2.2. [4+2] Annulation with electron-deficient olefins<!>2.3. [3+2] Annulation with imines<!>2.4. [4+2] Annulation with imines<!>2.5. [3+2]/[4+2] Annulation with ketones<!>2.6. Annulations with aldehydes<!>2.7. Miscellaneous<!>3. Enantioselective ... | <p>Trivalent phosphines and their derivatives are used widely in organic synthesis. Traditionally, they are applied as stoichiometric reagents in several name reactions, including the Wittig, Staudinger, and Mitsunobu reactions.1 In modern organic chemistry, organophosphorus compounds are often employed as ligands for ... | PubMed Author Manuscript |
Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker | Human fatty acid synthase (FASN) is a 270-kDa cytosolic dimeric enzyme that is responsible for palmitate synthesis. FASN is slowly emerging and rediscovered as a marker for diagnosis and prognosis of human cancers. Recent studies showed that FASN is an oncogene and inhibition of FASN effectively and selectively kill ca... | biochemistry,_molecular_biology,_and_pharmacology_of_fatty_acid_synthase,_an_emerging_therapeutic_ta | 7,547 | 108 | 69.87963 | Introduction<!>Structure and function of mammalian FASN<!>Regulation of FASN expression<!>Role of FASN in tumorigenesis and cancer cell proliferation<!>Role of FASN in prognosis and drug resistance<!>Mechanism of FASN action in cancers<!>FASN inhibitors<!>Cerulenin<!>C75<!>Olistat<!>Polyphenols/flavonoids<!>Triclosan<!... | <p>Altered metabolism in human cancers has long been recognized. The first observation of increased anaerobic glycolysis in cancer cells was made by Otto Warburg, the so called "Warburg effect" [1]. The "Warburg effect" has now become a hallmark of the transformed phenotype of cancer cells, and is thought to provide gr... | PubMed Author Manuscript |
Random Forest Refinement of the KECSA2 Knowledge-based Scoring Function for Protein Decoy Detection | Knowledge-based potentials generally perform better than physics-based scoring functions in detecting the native structure from a collection of decoy protein structures.Through the use of a reference state, the pure interactions between atom/residue pairs can be obtained through the removal of contributions from ideal-... | random_forest_refinement_of_the_kecsa2_knowledge-based_scoring_function_for_protein_decoy_detection | 3,986 | 258 | 15.449612 | Introduction<!>Building up the probability list for the proteins<!>Building up the ranking list for a decoy set<!>Decoy sets<!>Protein structure preparation<!>The KECSA2 potential<!>Machine learning and validation<!>(ii) Overall decoy sets training<!>Model accuracy (individual decoy set training)<!>Ranking of the nativ... | <p>According to the "thermodynamic hypothesis". 1 the native protein in its preferred milieu should adopt a structure that has the lowest Gibbs free energy. Hence, accurate energy functions are needed to solve the protein folding, the protein structure prediction, and protein design problems. Extant scoring functions c... | ChemRxiv |
11C=O Bonds Made Easily for Positron Emission Tomography Radiopharmaceuticals | The positron-emitting radionuclide carbon-11 (11C, t1/2 = 20.3 minutes) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation ... | 11c=o_bonds_made_easily_for_positron_emission_tomography_radiopharmaceuticals | 8,002 | 173 | 46.254335 | 1.1 Strategies for radiolabeling with carbon-11<!>1.2 Criteria for Practical Radiosynthesis with Carbon-11<!><!>1.2 Criteria for Practical Radiosynthesis with Carbon-11<!>2.1 Production and Handling of [11C]CO2<!>2.2 Methods for Radiotracer Synthesis<!>2.3 Impact<!>3. Radiochemistry with [11C]COCl2<!>3.1 Production and... | <p>The discovery and development of positron emission tomography (PET) radiopharmaceuticals demands an iterative approach that, even when informed by existing medicinal chemistry data and computational modeling, suffers from capricious trial-and-error based evaluation.1–4 While advances in radiochemical methods with ca... | PubMed Author Manuscript |
ShRNA-Mediated Gene Silencing of Lipoprotein Lipase Improves Insulin Sensitivity in L6 Skeletal Muscle Cells | In previous studies, we demonstrated that down-regulation of lipoprotein lipase in L6 muscle cells increased insulin-stimulated glucose uptake. In the current study, we used RNA interference technology to silence the LPL gene in L6 cells and generate a LPL-knock-down (LPL-KD) cell line. ShRNA transfected cells showed a... | shrna-mediated_gene_silencing_of_lipoprotein_lipase_improves_insulin_sensitivity_in_l6_skeletal_musc | 2,748 | 178 | 15.438202 | INTRODUCTION<!>Cell Culture and Differentiation<!>Silencing the LPL Gene<!>RNA Isolation and RT-PCR<!>Metabolic Studies in Cell Culture<!>Glycogen Synthesis Assay<!>Glucose Oxidation Assay<!>Fatty Acid Oxidation Assay<!>RESULTS<!>DISCUSSION<!> | <p>Lipoprotein lipase (LPL) is a lipolytic enzyme, required for the hydrolysis of triglycerides to glycerol and free fatty acids (FFA) [1,2]. LPL plays a key role in regulating the entry FFA into muscle and adipose cells, both insulin-responsive tissues [2,3]. LPL synthesis is regulated by various metabolic and endocri... | PubMed Author Manuscript |
CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation | An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RBR E3s ligate ubiquitin to substrates of neddylated cullin-RING E3s. The E3 ARIH2 has been implicated in ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s, includin... | cul5-arih2_e3-e3_ubiquitin_ligase_structure_reveals_cullin-specific_nedd8_activation | 8,730 | 150 | 58.2 | Introduction<!>Crystal structure of autoinhibited ARIH2<!>Overall E3-E3 assembly between ARIH2 and neddylated CRL5s<!>NEDD8-dependent allosteric remodeling of CUL5-RBX2<!>ARIH2-CUL5-RBX2 E3-E3act superdomain<!>Remodeled CUL5 groove cradles ARIH2 N-terminus<!>CRL5 neddylation removes barriers blocking ARIH2<!>General an... | <p>Ubiquitin (UB) and ubiquitin-like proteins (UBLs) are eukaryotic post-translational modifiers that determine the functions and fates of many proteins. Key facets of this regulation are: (1) E3 ligase-mediated linkage of the C-terminus of UB or UBL to a target protein; and (2) recognition of the modified protein by a... | PubMed Author Manuscript |
Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action | Resveratrol, a polyphenolic compound rich in grapes and red wine, has been reported to protect cells against oxidative damage and cell death by increasing cellular antioxidant/detoxification capacity. Cigarette smoking is a major risk factor for respiratory diseases and oxidative damage is implicated in its pathogenesi... | exacerbation_of_tobacco_smoke_mediated_apoptosis_by_resveratrol:_an_unexpected_consequence_of_its_an | 3,230 | 165 | 19.575758 | Introduction<!>Reagents<!>Cell culture and treatment<!>Preparation of cigarette smoke extracts (CSE)<!>Measurement of mRNA content<!>Western Blotting<!>Cell growth assay<!>Assay of caspase activity<!>Apoptosis assay<!>Statistical Analysis<!>Resveratrol increases expression of antioxidant genes<!>Resveratrol increased C... | <p>Resveratrol, a polyphenolic compound found in grapes, wine, berries, and herbal medicines, such as Polygonum cuspidatum, has been shown to exhibit various biochemical activities, such as regulation of the cell cycle (Hsieh and Wu, 1999), stimulation of endothelial nitric oxide synthase (Taubert and Berkels, 2003), a... | PubMed Author Manuscript |
SEIRAS Study of Chloride-Mediated Polyether Adsorption on Cu | Surface-enhanced infrared absorption spectroscopy is used to examine the co-adsorption of a selection of polyethers with Cl\xe2\x88\x92 under conditions relevant to superconformal Cu electrodeposition in CuSO4\xe2\x80\x93H2SO4 electrolytes. In 0.1 mol/L H2SO4, a potential-dependent mixed SO42\xe2\x88\x92\xe2\x80\x93H3O... | seiras_study_of_chloride-mediated_polyether_adsorption_on_cu | 13,062 | 167 | 78.215569 | INTRODUCTION<!>MATERIALS AND METHODS<!>RESULTS AND DISCUSSION<!>SO42\xe2\x88\x92 Adsorption on Cu in H2SO4.<!>SO42\xe2\x88\x92 Displacement by Cl\xe2\x88\x92.<!>PEG Adsorption on Cl\xe2\x88\x92-Terminated Cu.<!>Effect of Potential.<!>PEG Adsorption on Cu in the Absence of Cl\xe2\x88\x92.<!>Influence of Cl\xe2\x88\x92 A... | <p>Cu electrodeposition is a key process used in the fabrication of microelectronic circuitry ranging from deep submicrometer logic and memory interconnects to micron-scale through-silicon vias (TSV) for three-dimensional chip stacking. The success of the process stems from surfactant additives that enable void- and se... | PubMed Author Manuscript |
Open Drug Discovery Toolkit (ODDT): a new open-source player in the drug discovery field | BackgroundThere has been huge progress in the open cheminformatics field in both methods and software development. Unfortunately, there has been little effort to unite those methods and software into one package. We here describe the Open Drug Discovery Toolkit (ODDT), which aims to fulfill the need for comprehensive a... | open_drug_discovery_toolkit_(oddt):_a_new_open-source_player_in_the_drug_discovery_field | 1,952 | 189 | 10.328042 | Background<!>Implementation<!>Molecule formats<!>Interactions<!>Filtering<!>Docking<!>Scoring<!>Statistical methods<!>Results and discussions<!><!>Example 2: training and evaluating models for binding affinity datasets<!><!>Example 3: training classifiers to distinguish active from inactive compounds based on DUD-E<!><... | <p>Over the past decades, in silico drug discovery has become an important element augmenting classical medicinal chemistry and high throughput screening. Many novel computational chemistry methods were developed to aid researchers in discovering promising drug candidates. In recent years, much progress has been made i... | PubMed Open Access |
Formulating a new basis for the treatment against botulinum neurotoxin intoxication: 3,4-diaminopyridine prodrug design and characterization | Botulism is a disease characterized by neuromuscular paralysis and is produced from botulinum neurotoxins (BoNTs) found within the Gram positive bacterium Clostridium botulinum. This bacteria produces the most deadliest toxin known, with lethal doses as low as 1 ng/kg. Due to the relative ease of production and transpo... | formulating_a_new_basis_for_the_treatment_against_botulinum_neurotoxin_intoxication:_3,4-diaminopyri | 3,078 | 306 | 10.058824 | 1. Introduction<!>2.1 Materials<!>2.2 Enzyme inhibition assays<!>2.3 Enzyme-specific drug release assays<!>2.4 Sera half-life assays<!>2.5 Statistical analysis<!>3.1 Design of Prodrugs<!>3.2 Synthesis of Class I prodrugs<!>3.3 Synthesis of Class II prodrugs<!>3.4 Synthesis of Class III prodrugs<!>3.5 Inhibition, releas... | <p>Botulinum neurotoxins (BoNTs) produced from the Gram positive bacterium Clostridium botulinum are some of the deadliest toxins known to man1 with lethal doses as low as 1 ng per kg body weight being 10 million times more toxic than cyanide.2 Intoxication by BoNT produces generalized muscle weakness, and in severe ca... | PubMed Author Manuscript |
Hierarchical Porous Graphene–Iron Carbide Hybrid Derived From Functionalized Graphene-Based Metal–Organic Gel as Efficient Electrochemical Dopamine Sensor | A metal–organic gel (MOG) similar in constitution to MIL-100 (Fe) but containing a lower connectivity ligand (5-aminoisophthalate) was integrated with an isophthalate functionalized graphene (IG). The IG acted as a structure-directing templating agent, which also induced conductivity of the material. The MOG@IG was pyr... | hierarchical_porous_graphene–iron_carbide_hybrid_derived_from_functionalized_graphene-based_metal–or | 5,918 | 150 | 39.453333 | <!>Introduction<!>Reagents and Materials<!>Materials Synthesis<!>Materials Characterization<!>Magnetic Measurements<!>Sensing Measurements<!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!>Conclusions<!>... | <p>Metal-organic gel integrated with an isophthalate functionalized graphene gives rise to a hierarchically porous hybrid Fe/Fe3C/FeOx enveloped by graphene, which enables the highly selective sensing of the neurotransmitter dopamine in presence of ascorbic acid in ratios similar to those of blood serum.</p><!><p>Metal... | PubMed Open Access |
A diketopyrrolopyrrole dye-based dyad on a porous TiO2 photoanode for solar-driven water oxidation† | Dye-sensitised photoanodes modified with a water oxidation catalyst allow for solar-driven O2 evolution in photoelectrochemical cells. However, organic chromophores are generally considered unsuitable to drive the thermodynamically demanding water oxidation reaction, mainly due to their lack of stability upon photoexci... | a_diketopyrrolopyrrole_dye-based_dyad_on_a_porous_tio2_photoanode_for_solar-driven_water_oxidation† | 3,497 | 206 | 16.975728 | Introduction<!>Synthesis and characterisation<!>Photophysical properties<!>Electrochemical properties<!>Photoelectrochemistry under sacrificial conditions<!>Photoelectrochemical water oxidation<!>Oxygen quantification<!>Performance and comparison with state-of-the-art<!>Conclusions<!>Conflicts of interest | <p>The integration of a molecular dye and a water oxidation catalyst (WOC) onto an n-type metal oxide (e.g., titanium dioxide, TiO2) semiconductor (SC) film on a conductive substrate (e.g., fluorine-doped tin oxide, FTO), produces a dye-sensitised photoanode for visible light-driven O2 evolution in photoelectrochemical... | PubMed Open Access |
Towards quantitative point of care detection using SERS lateral flow immunoassays | The rapid detection of biomolecules in a point of care (POC) setting is very important for diagnostic purposes. A platform which can provide this, whilst still being low cost and simple to use, is paper-based lateral flow immunoassays (LFIA). LFIA combine immunology and chromatography to detect a target by forming an i... | towards_quantitative_point_of_care_detection_using_sers_lateral_flow_immunoassays | 2,869 | 260 | 11.034615 | Introduction<!><!>Raman mapping SERS-LFIA platform<!><!>Multiplexing from signal-resolved detection<!>Portable SERS-LFIA platform<!><!>All-in-one SERS-LFIA platform<!>Outlook<!><!>Funding<!>Conflict of interest | <p>Lateral flow immunoassays (LFIA) are paper-based devices used for the rapid detection of analytes and biomolecules in clinical practice. The advantages of LFIA are exploited when the test is used in the community because the platform offers a simple-to-use and cheap-to-produce test that can be readily produced at sc... | PubMed Open Access |
Synthesis, Mechanism of Formation, and Catalytic Activity of Xantphos Nickel \xcf\x80-Complexes | A general synthetic route to the first Xantphos nickel alkyne and alkene complexes has been discovered. Various Ni complexes were prepared and characterized. NMR experiments indicate benzonitrile undergoes ligand exchange with a Xantphos ligand of (Xant)2Ni, a compound that was previously believed to be unreactive. The... | synthesis,_mechanism_of_formation,_and_catalytic_activity_of_xantphos_nickel_\xcf\x80-complexes | 2,147 | 77 | 27.883117 | <p>Xantphos,1 a bidentate phosphine ligand with a rigid butterfly structure and a large bite angle, is a prolific ligand for a variety of nickel catalyzed reactions including hydrocyanation,2 alkylcyanation,3 cross coupling,4 conversion of ethylene into 1-butene,5 and more recently, cycloaddition.6 One limitation of th... | PubMed Author Manuscript | |
Simulating the Dynamics and Orientations of Spin Labeled Side Chains in a Protein-DNA Complex | Site-directed spin labeling, wherein a nitroxide side chain is introduced into a protein at a selected mutant site, is increasingly employed to investigate biological systems by electron spin resonance (ESR) spectroscopy. An understanding of the packing and dynamics of the spin label is needed to extract the biological... | simulating_the_dynamics_and_orientations_of_spin_labeled_side_chains_in_a_protein-dna_complex | 6,233 | 216 | 28.856481 | Introduction<!>DEER Experiments<!>MD Simulations<!>EcoRI DEER Measurements<!>MD Simulated Distance Distributions<!>Spin Label Dynamics and Conformers<!>Broad Utility of Approach<!>Conclusions | <p>Site-directed spin labeling (SDSL) for electron spin resonance (ESR) spectroscopy has now become a widely utilized method to obtain structural constraints, probe conformational changes, and monitor protein-protein and protein-ligand interactions.1–2 In such experiments the presence of the spin label contributes subs... | PubMed Author Manuscript |
UV-Induced Photodegradation of Naproxen Using a Nano γ-FeOOH Composite: Degradation Kinetics and Photocatalytic Mechanism | Naproxen (NPX) is one of the most common pharmaceutical and personal care products found in surface water, which is recalcitrant to degradation by biological treatment or complete removal via traditional sewage treatment processes. In this study, nanoscale γ-FeOOH was synthesized and characterized by X-ray diffraction,... | uv-induced_photodegradation_of_naproxen_using_a_nano_γ-feooh_composite:_degradation_kinetics_and_pho | 4,360 | 147 | 29.659864 | Introduction<!>Materials and Reagents<!>Synthesis of Nanostructured γ-FeOOH<!>Characterization of Nanostructured γ-FeOOH<!>Photoreaction Apparatus and Procedure<!><!>Photodegradation of NPX by γ-FeOOH<!>Langmuir–Hinshelwood Kinetics<!>Active Species Analysis<!>Characterization of γ-FeOOH<!><!>Characterization of γ-FeOO... | <p>With continuous improvements in anthropogenic living standards, the contamination of natural waterways has become an unavoidable and often neglected environmental issue. At present, however, water monitoring standards do not include pharmaceutical and personal care products (PPCPs), which are recalcitrant to biodegr... | PubMed Open Access |
Isotopic labeling of mammalian G protein-coupled receptors (GPCRs) heterologously expressed in Caenorhabditis elegans* | High-resolution structural determination and dynamic characterization of membrane proteins by nuclear magnetic resonance (NMR) require their isotopic labeling. Although a number of labeled eukaryotic membrane proteins have been successfully expressed in bacteria, they lack posttranslational modifications and usually ne... | isotopic_labeling_of_mammalian_g_protein-coupled_receptors_(gpcrs)_heterologously_expressed_in_caeno | 4,092 | 194 | 21.092784 | Introduction<!>Maintenance of worms and generation of transgenic (TG) worm lines<!>Stable isotope labeling of HB101<!>Stable isotope labeling of nematodes<!>Analysis of worm brood sizes<!>Analysis of growth rates<!>Analysis of egg hatching rate<!>Immunohistochemistry (IHC)<!>Immunoblotting<!>In vivo light-response assa... | <p>Drug design, lead generation and optimization are greatly facilitated if the structure of the biological target is known. This is particularly true when complexes between a ligand and target can be obtained. Although X-ray crystallography remains the current gold standard for structural determination, recent advance... | PubMed Author Manuscript |
Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity | Mutations that enhance LRRK2 protein kinase activity cause inherited Parkinson's disease. LRRK2 phosphorylates a group of Rab GTPase proteins, including Rab10 and Rab12, within the effector-binding switch-II motif. Previous work has indicated that the PARK16 locus, which harbors the gene encoding for Rab29, is involved... | endogenous_rab29_does_not_impact_basal_or_stimulated_lrrk2_pathway_activity | 11,530 | 251 | 45.936255 | Introduction<!>Reagents<!>Generation of MJFF rabbit monoclonal Rab29 total antibodies (MJF-30)<!>Other antibodies<!>Quantitative immunoblot analysis<!>Mice<!>Generation of Rab29 knock-out mice<!>Generation of Rab29 knock-out LRRK2[R1441C] and Rab29 knock-out VPS35[D620N] knock-in mice<!>Generation of transgenic Rab29 o... | <p>Autosomal dominant missense mutations that hyperactivate LRRK2 (leucine-rich repeat kinase 2) are one of the most common causes of familial Parkinson's disease (PD) [1–4]. Age of onset and progression of LRRK2-driven PD is virtually indistinguishable from sporadic PD, which comprises the vast majority of the patient... | PubMed Open Access |
Generating ampicillin-level antimicrobial peptides with activity-aware generative adversarial networks | Antimicrobial peptides are a potential solution to the threat of multidrug-resistant bacterial pathogens. Recently, deep generative models including generative adversarial networks (GANs) have been shown to be capable of designing new antimicrobial peptides. Intuitively, a GAN controls the probability distribution of g... | generating_ampicillin-level_antimicrobial_peptides_with_activity-aware_generative_adversarial_networ | 1,788 | 119 | 15.02521 | Introduction<!>Generative Model<!>Statistical Fidelity<!>Experimental Validation<!>Conclusion<!>Peptide Synthesis<!>MIC determination | <p>Antibiotic resistance is a serious and immediate threat against humanity, as currently available antibiotics become increasingly obsolete. The annual deaths due to antimicrobial resistance are expected to exceed 10 million by 2050. 1 Antimicrobial peptides (AMPs) are a possible solution to this problem. 2 They are c... | ChemRxiv |
Active Site Ring-Opening of a Thiirane Moiety and Picomolar Inhibition of Gelatinases | (\xc2\xb1)-2-[(4-Phenoxyphenylsulfonyl)methyl]thiirane 1 is a potent and selective mechanism-based inhibitor of the gelatinase sub-class of the zinc-dependent matrix metalloproteinase (MMP) family. Inhibitor 1 has excellent activity in in vivo models of gelatinase-dependent disease. We demonstrate that the mechanism of... | active_site_ring-opening_of_a_thiirane_moiety_and_picomolar_inhibition_of_gelatinases | 3,243 | 130 | 24.946154 | <!>Restoration of Activity to MMP-2 Inhibited by Thiirane 1<!>Solvolytic Chemistry of Thirane 1 and Key Analogues<!>A Kinetic Isotope Effect for MMP-2 Inhibition by Thiirane 1<!>Potent MMP-2 Inhibition by Thiol 7<!>Discussion | <p>The central position of the epoxide ring in organic synthesis derives from the ease of its synthesis, and the ability of Brønsted or Lewis acids to control its opening by nucleophiles. Thiiranes, three-membered rings containing a sulfur atom, are typically less reactive than epoxides. Due to their latent reactivity ... | PubMed Author Manuscript |
[Ag]2[B12Cl12] as a Catalyst in PhICl2 Mediated Chlorination | The weakly coordinating [B12Cl12] 2originates from a family of carboranes typically reserved for application in coordination chemistry. Here, we show its readily accessible Ag(I) salt, [Ag]2[B12Cl12], can be used as a catalyst in the PhICl2 mediated chlorination of arenes, alkenes, and alkynes. The promising activity d... | [ag]2[b12cl12]_as_a_catalyst_in_phicl2_mediated_chlorination | 1,764 | 69 | 25.565217 | <p>PhICl2, the first reported λ 3 -iodane compound, [1] is a versatile oxidant, primarily acting as a chlorinating agent representing a convenient substitute for Cl2. Cl2 is a highly corrosive, toxic gas, which in addition to being hazardous, is challenging to deliver in a stoichiometric fashion. Conversely, PhICl2 is ... | ChemRxiv | |
Superoxide Inhibits Guanine Nucleotide Exchange Factor (GEF) Action on Ras, but not on Rho, through Desensitization of Ras to GEF | Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GT... | superoxide_inhibits_guanine_nucleotide_exchange_factor_(gef)_action_on_ras,_but_not_on_rho,_through_ | 12,885 | 245 | 52.591837 | <!>Experimental Conditions<!>Generation and Quantification of O2\xe2\x80\xa2\xe2\x88\x92<!>Protein Sample Preparations<!>Kinetic Assay<!>DATA ANALYSES<!>RESULTS<!>Apparent Inhibition of the Oxidant-Mediated Catalytic Action of Cdc25 on wt Ras GTPase<!>Deconvolution of the Oxidant-Mediated Inhibition of the Catalytic Ac... | <p>The Ras and Rho families of small GTPases are subfamilies of the Ras superfamily.1 The Ras family of small GTPases includes Harvey Ras (HRas), Neuroblastoma Ras, and Kirsten Ras.2 Ras-dependent cellular signals control cell growth and division.3,4 Rac1 and other proteins, such as RhoA, RhoC, and Cdc42, belong to the... | PubMed Author Manuscript |
Chiroptical inversion of a planar chiral redox-switchable rotaxane | A tetrathiafulvalene (TTF)-containing crown ether macrocycle with C s symmetry was designed to implement planar chirality into a redox-active [2]rotaxane. The directionality of the macrocycle atom sequence together with the non-symmetric axle renders the corresponding [2]rotaxane mechanically planar chiral. Enantiomeri... | chiroptical_inversion_of_a_planar_chiral_redox-switchable_rotaxane | 2,190 | 126 | 17.380952 | Introduction<!>Synthesis and characterisation<!>Optoelectronic properties<!>Enantiomer separation on chiral HPLC and CD spectroscopy<!>Conclusions | <p>Evidenced by the homochirality in our biosphere, [1][2][3] chirality is a fundamental principle, which governs the molecular recognition and activity of virtually all biomolecules. Therefore, gaining control over the preferred isomer of a molecule or an assembly by carefully designing a molecular system is a worthwh... | Royal Society of Chemistry (RSC) |
Visualizing and trapping transient oligomers in amyloid assembly pathways | Oligomers which form during amyloid fibril assembly are considered to be key contributors towards amyloid disease. However, understanding how such intermediates form, their structure, and mechanisms of toxicity presents significant challenges due to their transient and heterogeneous nature. Here, we discuss two differe... | visualizing_and_trapping_transient_oligomers_in_amyloid_assembly_pathways | 6,174 | 150 | 41.16 | <!>Introduction<!>Solution NMR<!>Single particle and non-ensemble averaged methods<!>Trapping transient oligomers to facilitate the characterization of amyloid self-assembly<!>Sample preparation strategies<!>Using antibodies to probe the structure and toxicity of oligomers<!><!>Stabilizing oligomers using non-covalent ... | <p>Methods to study structure, toxicity, and kinetics of transient amyloid oligomers.</p><p>NMR and single particle methods can characterize lowly-populated oligomers.</p><p>Chemical tools/antibodies stabilize oligomers for structural and toxicity studies</p><p>A combination of methods is needed to fully characterize a... | PubMed Open Access |
An aqueous electrolyte of the widest potential window and its superior capability for capacitors | A saturated aqueous solution of sodium perchlorate (SSPAS) was found to be electrochemically superior, because the potential window is remarkably wide to be approximately 3.2 V in terms of a cyclic voltammetry. Such a wide potential window has never been reported in any aqueous solutions, and this finding would be of h... | an_aqueous_electrolyte_of_the_widest_potential_window_and_its_superior_capability_for_capacitors | 5,249 | 200 | 26.245 | <!>Results<!>Capability of SSPAS as an electrolyte in graphite-based capacitors.<!>Effect of metal oxides for the graphite-based capacitor.<!>Discussion<!>Conclusion<!>Methods | <p>It has been generally understood that aqueous electrolytes have many advantages compared with non-aqueous solvents with respect to electrochemical behaviour as well as economic and environmental impacts. However, there exists serious disadvantage in aqueous electrolytes that water is easily electrolyzed to generate ... | Scientific Reports - Nature |
Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat Can Generate Potent MMP Inhibitory Activity without Inducing Cytotoxicity | The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a cyclam–marimastat conjugate and its metal complexes are described. The conjugate, synthesized with a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (“click” reaction), contains two zinc-binding groups (ZBGs). The metal complexation behavio... | incorporation_of_bulky_and_cationic_cyclam-triazole_moieties_into_marimastat_can_generate_potent_mmp | 3,205 | 176 | 18.210227 | Introduction<!><!>Introduction<!><!>Synthesis of the cyclam–marimastat conjugate 4<!><!>Synthesis of the cyclam–marimastat conjugate 4<!>Metal complexation<!><!>Metal complexation<!><!>Metal complexation<!><!>Metal complexation<!><!>Metal complexation<!>MMP inhibition studies<!><!>MMP inhibition studies<!>Cytotoxicity<... | <p>Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases capable of degrading extracellular matrix constituents.1 These enzymes play a pivotal role in a variety of physiological processes, including tissue remodeling, wound healing, embryonic development and angiogenesis.2 Overexpression of MMPs has been ... | PubMed Open Access |
CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters | Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangula... | crispr-cas9_strategy_for_activation_of_silent_streptomyces_biosynthetic_gene_clusters | 3,573 | 69 | 51.782609 | <!>Reagents and Media<!>Strains and Growth conditions<!>Construction of genome editing plasmids<!>Interspecies conjugation<!>Validation of promoter knock-in and genome editing<!>RNA isolation and Real-time quantitative PCR (RT-qPCR)<!>Fermentation, ethyl acetate extraction and LC-MS analysis metabolites from wild type ... | <p>Microbial natural products are a rich source of pharmaceutical agents and current advances in genomics have unveiled a vast source of potential unexplored BGCs. Because majority of encoded metabolites of these BGCs are undetectable using current analytical methods due to minimal or zero BGC expression under laborato... | PubMed Author Manuscript |
Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer | BackgroundThis phase 1 study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287) Process 2, a new formulation of fully human anti-HER3 monoclonal antibody in combination with erlotinib, an epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) in prior chemotherapy tr... | phase_1_study_of_new_formulation_of_patritumab_(u3-1287)_process_2,_a_fully_human_anti-her3_monoclon | 2,761 | 236 | 11.699153 | Introduction<!>Patient eligibility<!>Study design and evaluation<!>Pharmacokinetics<!>Biomarkers<!>Statistical method<!>Patient characteristics<!><!>Safety and tolerability<!><!>Safety and tolerability<!>Pharmacokinetics<!><!>Efficacy<!>Biomarker analysis (serum HER3 and heregulin)<!><!>Discussion | <p>The human epidermal growth factor receptor-3 (HER3) is a member of the HER (EGFR/ErbB) receptor family consisting of four closely related type 1 transmembrane receptors (EGFR, HER2, HER3, and HER4). HER receptors are part of a complex signaling network intertwined with the Ras/Raf/MAPK, PI3K/AKT, JAK/STAT, and PKC s... | PubMed Open Access |
Patterned Dried Blood Spot Cards for Improved Sampling of Whole Blood | Dried blood spot (DBS) cards perform many functions for sampling blood that is intended for subsequent laboratory analysis, which include: (i) obviating the need for a phlebotomist by using fingersticks, (ii) enhancing the stability of analytes at ambient or elevated environmental conditions, and (iii) simplifying tran... | patterned_dried_blood_spot_cards_for_improved_sampling_of_whole_blood | 3,920 | 248 | 15.806452 | Introduction<!>Experimental Design<!>Effects of Evaporation on the Quantitation of Hemoglobin<!>Estimation of Sample Volume in 6-mm Paper Punch<!>pDBS Cards Fill Independent of Hematocrit Value<!>Quantitation of Sodium by ICP-AES<!>Quantitation of Amino Acids by HPLC<!>Conclusions<!>Conflicts of Interest | <p>Blood is a complex matrix, comprising cellular and liquid fractions, that contains a wealth of diagnostically relevant biomarkers, which are inclusive of the cells themselves (e.g., neutrophil count), DNA/RNA (e.g., endogenous or from pathogens), and myriad solutes in plasma (e.g., proteins, metabolites, free amino ... | ChemRxiv |
Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis** | Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein–protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be... | stereochemical_assignment_of_the_protein–protein_interaction_inhibitor_jbir-22_by_total_synthesis** | 1,824 | 104 | 17.538462 | <!> | <p>Natural products that contain the tetramic acid motif have been studied extensively, and their complexity and biological profiles have led to several total syntheses.[1] For example, equisetin, a close structural analogue of the compounds studied here, has been prepared.[1a–c] However, the synthesis of members of a ... | PubMed Open Access |
The Effects of Storage Conditions on Lycopene Content and Color of Tomato Hot Pot Sauce | Tomato hot pot sauce (THPS) at different storage temperatures (0, 25, and 37°C) and with two kinds of packaging for 120 days was investigated in this study. High performance liquid chromatography was employed for detecting lycopene and 5-hydroxymethylfurfural (HMF). The changes of lycopene and HMF during storage were r... | the_effects_of_storage_conditions_on_lycopene_content_and_color_of_tomato_hot_pot_sauce | 3,315 | 186 | 17.822581 | 1. Introduction<!>2.1. Chemicals<!>2.2. Tomato Hot Pot Sauce and Preparation<!>2.3. Color Analyses<!>2.4. Lycopene Analysis<!>2.5. 5-Hydroxymethylfurfural Analysis<!>2.6. Ascorbic Acid Analysis<!>2.7. Statistical Analysis<!>3.1. Changes of Lycopene Content<!>3.2. Changes of HMF Content<!>3.3. Changes of Ascorbic Acid C... | <p>Hot pot is one of the most popular Chinese foods in China and has spread all over the world since it is very easy to keep its authentic taste. The core of hot pot taste is the hot pot sauce, which is used to prepare the base soup of hot pot. In the last decade, hot pot sauce has been upgraded from handmade in small ... | PubMed Open Access |
Expanding the concept of chemically programmable antibodies to RNA-aptamers: a novel class of chemically programmed biotherapeutics | Chemically programmed antibodies represent a new class of biologic drugs that acquire their specificity through chemistry rather than through biology. To date, this approach has used small molecules and peptides to direct targeting and to extend the pharmacokinetics and otherwise enhance the biological function of the ... | expanding_the_concept_of_chemically_programmable_antibodies_to_rna-aptamers:_a_novel_class_of_chemic | 1,453 | 282 | 5.152482 | <p>Key to understanding of the concept of chemically programmable antibodies is the catalytic antibody 38C2 that efficiently catalyzes aldol and related reactions through an enamine mechanism.[1] The reactivity of this and related antibody aldolases is provided by an exceptionally nucleophilic lysine residue located on... | PubMed Author Manuscript | |
Experimental validation of FINDSITEcomb virtual ligand screening results for eight proteins yields novel nanomolar and micromolar binders | BackgroundIdentification of ligand-protein binding interactions is a critical step in drug discovery. Experimental screening of large chemical libraries, in spite of their specific role and importance in drug discovery, suffer from the disadvantages of being random, time-consuming and expensive. To accelerate the proce... | experimental_validation_of_findsitecomb_virtual_ligand_screening_results_for_eight_proteins_yields_n | 6,368 | 213 | 29.896714 | Background<!>Results<!><!>E. coli dihydrofolate reductase (DHFR)<!>Protein tyrosine phosphatases (PTP)<!>Ubiquitin-modifying enzyme (UCE)<!>Tryptophanyl tRNA synthetase (TrpRS)<!>Thioredoxin peroxidase2 (TP2), cAMP-dependent protein kinase (cDPK) and nucleosome assembly protein 1(NAP1)<!>Discussion<!>Conclusions<!>Deta... | <p>Traditional experimental approaches to drug discovery rely on two different strategies [1]. The first selects a reliable therapeutic target that might be essential for an organism's or cell's survival, and then, using chemical library screening, potential leads that bind to and modulate the activity of the target in... | PubMed Open Access |
Omeprazole Induces NAD(P)H Quinone Oxidoreductase 1 via Aryl Hydrocarbon Receptor-Independent Mechanisms: Role of the Transcription Factor Nuclear Factor Erythroid 2\xe2\x80\x93Related Factor 2 | Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additional... | omeprazole_induces_nad(p)h_quinone_oxidoreductase_1_via_aryl_hydrocarbon_receptor-independent_mechan | 2,019 | 199 | 10.145729 | Introduction<!>Cell culture and treatment<!>Cell viability assay<!>Determination of Functional Activation of AhR<!>Real-time RT-PCR assays<!>Western Blot Assays<!>Small interfering RNA (siRNA) transfections<!>Analyses of data<!>Results and Discussion | <p>The aryl hydrocarbon receptor (AhR) is a member of basic - helix – loop – helix / PER – ARNT – SIM family of transcriptional regulators [1–3]. In humans, the AhR is highly expressed in the lungs, thymus, kidney and liver [4]. The AhR is predominantly cytosolic, localized in a core complex comprising two molecules of... | PubMed Author Manuscript |
An enzyme-free molecular catalytic device: dynamically self-assembled DNA dendrimers for <i>in situ</i> imaging of microRNAs in live cells | DNA has become a promising material to construct high-order structures and molecular devices owing to its sequence programmability. Herein, a DNA machine based on branched catalytic hairpin assembly (bCHA) is introduced for dynamic self-assembly of DNA dendrimers. For this system, a Y-shaped hairpin trimer tethered wit... | an_enzyme-free_molecular_catalytic_device:_dynamically_self-assembled_dna_dendrimers_for_<i>in_situ< | 3,988 | 237 | 16.827004 | Introduction<!>Principle of bCHA<!>Native polyacrylamide gel electrophoresis (PAGE)<!>Amplication biosensing of microRNA<!>Amplication efficiency of bCHA<!>In situ imaging of miR-155 in live cells<!>Conclusions<!>Native polyacrylamide gel electrophoresis (PAGE)<!>Morphology characterization<!>Dynamic light scattering... | <p>Deoxyribonucleic acids (DNAs) have been considered as promising building blocks to fabricate a variety of nanostructures and devices owing to their sequence programmability and specic recognition properties. 1 The applications of DNAs as engineering materials provide a solid foundation for the development of DNA na... | Royal Society of Chemistry (RSC) |
Structural and biochemical studies of the glucuronoyl esterase OtCE15A illuminate its interaction with lignocellulosic components | Glucuronoyl esterases (GEs) catalyze the cleavage of ester linkages between lignin and glucuronic acid moieties on glucuronoxylan in plant biomass. As such, GEs represent promising biochemical tools in industrial processing of these recalcitrant resources. However, details on how GEs interact and catalyze degradation o... | structural_and_biochemical_studies_of_the_glucuronoyl_esterase_otce15a_illuminate_its_interaction_wi | 6,646 | 247 | 26.906883 | Introduction<!>Kinetic characterization of catalytic residue substitutions<!><!>Catalytic OtCE15A variants in complex with GlcA and benzyl glucuronoate<!><!>Catalytic OtCE15A variants in complex with GlcA and benzyl glucuronoate<!><!>Catalytic OtCE15A variants in complex with GlcA and benzyl glucuronoate<!><!>Catalytic... | <p>Glucuronyl esterases (GEs)4 are enzymes able to cleave ester linkages connecting lignin to glucuronoxylan in the plant cell wall. GEs are promising tools for improving biomass-processing technologies by reducing the recalcitrance of so-called lignin-carbohydrate complexes (LCCs) in lignocellulosic biomass (1). Since... | PubMed Open Access |
Controlling the rotation modes of hematite nanospindles by dynamic magnetic fields | The magnetic field-induced actuation of colloidal nanoparticles has enabled tremendous recent progress towards microrobots, suitable for a variety of applications including targeted drug delivery, environmental remediation or minimally invasive surgery.Further size reduction to the nanoscale requires enhanced control o... | controlling_the_rotation_modes_of_hematite_nanospindles_by_dynamic_magnetic_fields | 3,024 | 130 | 23.261538 | Introduction<!>Results and Discussion<!>Conclusion | <p>Field-driven actuation on magnetic particles builds the foundation of various intriguing applications, including self-propelling particles in active matter, 1,2 mixers in microfluidics, 3 and viscosity probes in nanorheology, 4 but also aspects based on structure formation, such as field-induced self-organization [5... | ChemRxiv |
Insights into MiRNA Regulation of the Human Glycome | Glycosylation is an intricate process requiring the coordinated action of multiple proteins, including glycosyltransferases, glycosidases, sugar nucleotide transporters and trafficking proteins. Work by several groups points to a role for microRNA (miRNA) in controlling the levels of specific glycosyltransferases invol... | insights_into_mirna_regulation_of_the_human_glycome | 2,544 | 120 | 21.2 | Introduction<!>Glycogene target analysis and pathway annotation<!>General Analysis of Glycogene Regulation<!>Predicted Regulatory Hubs in N-linked Glycosylation Pathway<!>Predicted Regulatory Hubs in O-linked Glycosylation Pathway<!>Predicted Regulatory Hubs Affecting Terminal Glycan Epitopes on both N- and O-linked Gl... | <p>The cell surface is coated with glycans, complex biopolymers that form a critical interface with the extracellular world and inform diverse processes from immune recognition to cancer metastasis. Glycosylation is an intricate process requiring the integrated action of multiple proteins, including glycosylation enzym... | PubMed Author Manuscript |
Parallel Synthesis of An Oligomeric Imidazole-4,5-dicarboxamide Library | A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate non-polar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala),... | parallel_synthesis_of_an_oligomeric_imidazole-4,5-dicarboxamide_library | 2,775 | 114 | 24.342105 | Introduction<!>Results and Discussion<!>Conclusion | <p>The design and preparation of compound libraries for application in high-throughput screening is a well-known approach to hit identification in drug discovery research.1,2 The library design criteria are generally target dependent, with the choice of scaffold or building blocks determined by considering known bioact... | PubMed Author Manuscript |
Organocatalytic Stereoselective Synthesis of Fluorinated 3,3\xe2\x80\xb2-Linked Bisoxindoles | A highly diastereoselective organocatalytic method that produces 3-fluoro-3\xe2\x80\xb2-hydroxy-3,3\xe2\x80\xb2-bisoxindoles and the corresponding 3-fluoro-3\xe2\x80\xb2-amino derivatives having two adjacent chirality centers from fluorooxindoles and isatins in high yields is described. The reaction occurs in protic so... | organocatalytic_stereoselective_synthesis_of_fluorinated_3,3\xe2\x80\xb2-linked_bisoxindoles | 5,163 | 52 | 99.288462 | <!>Experimental Section<!>General Procedure<!>3-Fluoro-3\xe2\x80\xb2-hydroxy-1-phenyl-[3,3\xe2\x80\xb2-biindoline]-2,2\xe2\x80\xb2-dione<!>Large Scale Synthesis of 3<!>5\xe2\x80\xb2-Chloro-3-fluoro-3\xe2\x80\xb2-hydroxy-1-phenyl-[3,3\xe2\x80\xb2-biindoline]-2,2\xe2\x80\xb2-dione<!>5\xe2\x80\xb2-Bromo-3-fluoro-3\xe2\x80... | <p>The unique physicochemical properties and widespread use of fluorinated organic compounds in the health sciences continues to attract considerable attention. Numerous studies have shown that incorporation of fluorine can improve the therapeutic index of biologically active compounds.1 The introduction of synthetic m... | PubMed Author Manuscript |
Dialumenes – aryl <i>vs.</i> silyl stabilisation for small molecule activation and catalysis | Main group multiple bonds have proven their ability to act as transition metal mimics in the last few decades.However, catalytic application of these species is still in its infancy. Herein we report the second neutral NHC-stabilised dialumene species by use of a supporting aryl ligand (3). Different to the trans-plana... | dialumenes_–_aryl_<i>vs.</i>_silyl_stabilisation_for_small_molecule_activation_and_catalysis | 5,451 | 165 | 33.036364 | Introduction<!>Synthesis of aryl-stabilised dialumene<!>Computational discussion of aryl-stabilised dialumene<!>Reactivity of dialumenes<!>Small molecule activation<!>Catalysis<!>CO 2 hydroboration<!>Conclusions<!>Conflicts of interest | <p>The ability to isolate and stabilise complexes containing metalmetal bonds is of fundamental interest, providing both experimental and theoretical insights into the intrinsic nature of the metal centre. 1 Since the discovery that the so-called 'double bond rule' could be broken in the beginning of the last quarter o... | Royal Society of Chemistry (RSC) |
Mechanism of the Intramolecular Claisen Condensation Reaction Catalyzed by MenB, a Crotonase Superfamily Member\xe2\x80\xa0 | MenB, the 1,4-dihydroxy-2-naphthoyl-CoA synthase from the bacterial menaquinone biosynthesis pathway, catalyzes an intramolecular Claisen condensation (Dieckmann reaction) in which the electrophile is an unactivated carboxylic acid. Mechanistic studies on this crotonase family member have been hindered by partial activ... | mechanism_of_the_intramolecular_claisen_condensation_reaction_catalyzed_by_menb,_a_crotonase_superfa | 6,084 | 313 | 19.4377 | <!>Experimental Procedures<!>Ligand synthesis<!>Preparation of wild-type and mutant MenB enzymes<!>apo-ecMenB and OSB-NCoA:ecMenB<!>mtMenB<!>Enzyme kinetics<!>Active site disorder<!>The OSB-NCoA substrate analogue<!>Structure of the ecMenB:OSB-NCoA complex<!>Conformation of the A-loop<!>Binding mode of the substrate<!>... | <p>Menaquinone (vitamin K2; Figure 1) is a polyisoprenylated naphthoquinone that functions as a redox active cofactor in the electron transport chain of most Gram positive and some Gram negative bacteria (1–2). Although humans utilize menaquinone and the related naphthoquinone vitamin K1 (phylloquinone; Figure 1) for t... | PubMed Author Manuscript |
CO2 and Water Activation on Ceria Nanocluster Modified TiO2 Rutile (110) | Surface modification of TiO2 with metal oxide nanoclusters is a strategy for the development of new photocatalyst materials. We have studied modification of the (110) surface of rutile TiO2 with ceria nanoclusters using density functional theory corrected for on-site Coulomb interactions (DFT+U). We focus on the impact... | co2_and_water_activation_on_ceria_nanocluster_modified_tio2_rutile_(110) | 5,960 | 211 | 28.246445 | INTRODUCTION<!>METHODOLOGY<!>The singlet-triplet excitation energy:<!>Stoichiometric CeO2-modified TiO2 structures<!>Reduction of CeO2-rutile by oxygen vacancy formation<!>Modelling charge separation upon photoexcitation.<!>CO2 adsorption at the reduced nanocluster-surface composites.<!>H2O adsorption at the reduced na... | <p>Since the seminal paper by Fujishima and Honda in 1972, 1 titanium dioxide, TiO2, has remained at the forefront of photocatalysis research due to its abundance, low-cost, nontoxicity and robustness under operating conditions. The large bandgap (>3 eV) means that TiO2 is UV active so that extending light absorption t... | ChemRxiv |
NF-\xce\xbaB as a Therapeutic Target in Inflammatory-Associated Bone Diseases | Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a... | nf-\xce\xbab_as_a_therapeutic_target_in_inflammatory-associated_bone_diseases | 9,097 | 231 | 39.380952 | 1. INTRODUCTION<!>2.1 Inflammation<!>2.1.1 Acute vs Chronic Inflammation<!>2.1.2 Proinflammatory and Antiinflammatory Functions of Macrophages<!>2.2 Acute Inflammation-Associated Bone Disorders<!>2.3.1 Fracture Nonunion<!>2.3.2 Periprosthetic Osteolysis<!>2.3.3 Senile Osteoporosis<!>3. INFLAMMATION AND NF-\xce\xbaB SIG... | <p>Bone is the major component of the skeletal system and provides physical support and protection of the body, calcium metabolism, and endocrine regulation, and it facilitates the hematopoietic system in bone marrow. Bone remodeling is a dynamic process that continues throughout life and involves bone formation and bo... | PubMed Author Manuscript |
Probing Protein Shelf Lives from Inverse Mean First Passage Times | Protein aggregation is investigated theoretically via protein turnover, misfolding, aggregation and degradation. The Mean First Passage Time (MFPT) of aggregation is evaluated within the framework of Chemical Master Equation (CME) and pseudo first order kinetics with appropriate boundary conditions. The rate constants ... | probing_protein_shelf_lives_from_inverse_mean_first_passage_times | 1,916 | 134 | 14.298507 | <p>Most proteins have been evolved to spontaneously fold to their native states, which determine their functional specificity and diversity. 1,2 Any phenotypic or genotypic variations may induce abnormal amino acid modifications and cause protein misfolding. [3][4][5] Misfolded proteins disrupt normal cellular function... | ChemRxiv | |
A fluorescence-based assay for N-myristoyltransferase activity | N-myristoylation is the irreversible attachment of a C14-fatty acid, myristic acid, to the N-terminal glycine of a protein via formation of an amide bond. This modification is catalyzed by myristoyl-CoA : protein N-myristoyltransferase (NMT), an enzyme ubiquitous in eukaryotes that is up-regulated in several cancers. H... | a_fluorescence-based_assay_for_n-myristoyltransferase_activity | 1,214 | 100 | 12.14 | <p>Myristoyl-coenzyme A : protein N-myristoyltransferase (N-myristoyltransferase, NMT) is a ubiquitous enzyme in eukaryotes that catalyzes co- and post-translational transfer of a C14 saturated fatty acid (myristic acid) from myristoyl-coenzyme A (myristoyl-CoA) to the N-terminal glycine residue of target proteins [1] ... | PubMed Author Manuscript | |
From machine learning to transfer learning in laser-induced breakdown spectroscopy analysis of rocks for Mars exploration | surface asperity on the hydrogen emission line has been investigated 11 . Our recently published work 12 observed and analyzed the performance of a machine learning-based model 13 , trained with a set of pressed rock powder pellets for total alkali-silica (TAS) classification 14 of rocks in their natural state. A signi... | from_machine_learning_to_transfer_learning_in_laser-induced_breakdown_spectroscopy_analysis_of_rocks | 5,750 | 735 | 7.823129 | <!>OPEN<!>Samples, experimental setup and measurement protocol<!>Experimental setup.<!>Data treatment method<!>Data pretreatment.<!>Transfer learning-based calibration model training. A transfer learning model training algorithm<!>Results and discussion<!>Conclusions | <p>Although the matrix effects correspond to a general issue in LIBS, they become accentuated in the case of rock analysis for Mars exploration, because of the large variation of rock compositions leading to the chemical matrix effect, and the difference in surface physical properties between laboratory standards (in p... | Scientific Reports - Nature |
Recent Progress in Decarboxylative Oxidative Cross‐Coupling for Biaryl Synthesis | The beginning of the 21st century has seen tremendous growth in the field of decarboxylative activation. Benzoic acid derivatives are now recognised as atom‐economic alternatives to traditional cross‐coupling partners, and they also benefit from being inexpensive, readily available and shelf‐stable reagents. In this mi... | recent_progress_in_decarboxylative_oxidative_cross‐coupling_for_biaryl_synthesis | 4,326 | 87 | 49.724138 | 1. Introduction<!>1.1. Brief History of Decarboxylative Oxidative Coupling<!><!>2. Protodecarboxylation: Trends in Decarboxylation Aided by Transition Metals<!>2.1. [Cu] Systems<!><!>2.2. [Pd] Systems<!><!>2.2. [Pd] Systems<!>2.3. [Ag] Systems<!><!>2.3. [Ag] Systems<!><!>2.4. ortho Effect in Transition‐Metal‐Catalysed ... | <p>The advent of traditional cross‐coupling reactions – coupling between aryl halides and organometallic reagents – revolutionized thoughts relating to the construction of C–C bonds.1 More recent developments in the areas of C–H activation and decarboxylative activation have looked to improve the atom economy of these ... | PubMed Open Access |
Photonic Crystal-Enhanced Fluorescence Imaging Immunoassay for Cardiovascular Disease Biomarker Screening with Machine Learning Analysis | When myocardial walls experience stress due to cardiovascular diseases, like heart failure, hormone N-terminal pro-B-type natriuretic peptide (NT-proBNP) is secreted into the blood. Early detection of NT-proBNP can assist diagnosis of heart failure and enable early medical intervention. A simple, cost-effective detecti... | photonic_crystal-enhanced_fluorescence_imaging_immunoassay_for_cardiovascular_disease_biomarker_scre | 4,092 | 249 | 16.433735 | Introduction<!>Diatom-based NT-proBNP Sensor Fabrication<!>Fluorescence Image Preprocessing and Processing<!>Statistical Regression Calibration Curve Creation<!>Qualitative Screening Procedure<!>Cardiovascular Disease Biosensing Mechanism<!>Average Intensity Analysis<!>Quantitative Statistical Regression<!>Qualitative ... | <p>According to the American Heart Association, in 2009, one in nine deaths cited heart failure (HF) as a contributing cause and in 2016, about 5.7 million Americans suffered from HF (Mozzafarian et al., 2016). Total direct medical costs of HF in the US are projected to be $42.9 billion by 2020 (Heindenreich et al. 201... | PubMed Author Manuscript |
Polymorphism,
Structure, and Nucleation of Cholesterol·H2O at Aqueous
Interfaces and in Pathological Media: Revisited
from a Computational Perspective | We revisit the important issues of polymorphism, structure, and nucleation of cholesterol·H2O using first-principles calculations based on dispersion-augmented density functional theory. For the lesser known monoclinic polymorph, we obtain a fully extended H-bonded network in a structure akin to that of hexagonal ice. ... | polymorphism,_structure,_and_nucleation_of_cholesterol·h2o_at_aqueous_interfaces_and_in_pathological | 5,753 | 233 | 24.690987 | Introduction<!>Density Functional Theory (DFT) Optimization
of the Triclinic
Polymorph of Cholesterol·H2O<!><!>DFT Optimization of the Monoclinic Crystal Structure of Cholesterol·H2O<!><!>DFT Optimization of the Monoclinic Crystal Structure of Cholesterol·H2O<!>Comparison of the Two Computed Cholesterol·H2O Polymorphs
... | <p>Cholesterol, the most
abundant sterol in mammalian cells, is a
vital component of cell membranes and is essential for cell viability.1 The cholesterol molecule consists of one hydroxyl
group attached to a rigid steroid tetracyclic moiety, terminating
with a flexible hydrocarbon chain (Scheme 1A).2 Cholesterol
is pra... | PubMed Open Access |
Catalytic Decarboxylative Radical Sulfonylation | Sulfones are not only important structural motifs in pharmaceuticals and agrochemicals but also versatile intermediates in organic synthesis. However, C(sp 3 )-sulfonyl bond formations remain underdeveloped. In this issue of Chem, Li and co-workers demonstrate that the merger of photo-organocatalysis and copper-catalys... | catalytic_decarboxylative_radical_sulfonylation | 2,303 | 76 | 30.302632 | INTRODUCTION<!>RESULTS AND DISCUSSION<!>Conclusions<!>SUPPLEMENTAL INFORMATION | <p>Sulfones are ubiquitous in nature. They possess a wide variety of biological activities and thus serve as important structural motifs in pharmaceuticals and agrochemicals. For example, bicalutamide (CASODEX, AstraZeneca's blockbuster drug) is an orally active, nonsteroidal anti-androgen for the treatment of prostate... | Chem Cell |
Residue-Based Preorganization of BH3-Derived \xce\xb1/\xce\xb2-Peptides: Modulating Affinity, Selectivity and Proteolytic Susceptibility in \xce\xb1-Helix Mimics | We report progress toward a general strategy for mimicking the recognition properties of specific \xce\xb1-helices within natural proteins through the use of oligomers that are less susceptible than conventional peptides to proteolysis. The oligomers contain both \xce\xb1- and \xce\xb2-amino acid residues, with the den... | residue-based_preorganization_of_bh3-derived_\xce\xb1/\xce\xb2-peptides:_modulating_affinity,_select | 5,381 | 205 | 26.24878 | Introduction<!>Development of a constrained \xce\xb2-amino acid with an acidic side chain<!>Binding of BH3-mimetic \xce\xb1/\xce\xb2-peptides to Bcl-xL and Mcl-1<!>Engagement of an apoptosis signaling network by BH3-mimetic \xce\xb1/\xce\xb2-peptides<!>Proteolytic susceptibilities<!>Discussion<!>Conclusions<!>Materials... | <p>α-Helices play prominent roles in protein associations. In some cases, one partner's contribution to the binding interface is comprised entirely of an α-helical segment, while in other cases the α-helix is part of a more complex recognition surface, as documented in comprehensive structural surveys by Arora et al.1-... | PubMed Author Manuscript |
Downstream processing of Isochrysis galbana: a step towards microalgal biorefinery | An algae-based biorefinery relies on the efficient use of algae biomass through its fractionation of several valuable/bioactive compounds that can be used in industry. If this biorefinery includes green platforms as downstream processing technologies able to fulfill the requirements of green chemistry, it will end-up w... | downstream_processing_of_isochrysis_galbana:_a_step_towards_microalgal_biorefinery | 5,845 | 250 | 23.38 | Introduction<!>Chemicals and samples<!>2.2.1.<!>Conventional extraction method.<!>Total carotenoid and chlorophyll determination<!>Analysis of carotenoids and chlorophylls by HPLC-DAD<!>Identification of carotenoids by HPLC-APCI-MS/MS<!>Analysis of lipid class compositions by HPLC-evaporative light scattering detection... | <p>A biorefinery involves biomass conversion processes and equipment to produce fuel, power, and added-value chemicals from organic materials 1 such as renewable resources or microalgae. Microalgae are among the most promising raw materials for the sustainable supply of commodities and the use of algae. 2,3 They use li... | Royal Society of Chemistry (RSC) |
Effects of π-Extension on Pyrrole Hemithioindigo Photoswitches | The most red-shifted hemithioindigo photoswitches have been identified through systematic introduction of aryl units to a parent pyrrole hemithioindigo photoswitch. Increasing the size of the 5'-aryl substituent is ineffective at producing further redshifted chromophores. A second generation of 3',5'-diarylated photosw... | effects_of_π-extension_on_pyrrole_hemithioindigo_photoswitches | 3,804 | 64 | 59.4375 | Introduction:<!>Results and Discussion<!>Conclusion<!>General Experimental Procedure<!>Materials<!>Instrumentation<!>General Procedure for Suzuki coupling with solid aryl bromides<!>General Procedure for Suzuki coupling with liquid aryl bromides<!>General Procedure for synthesis of ArylPyrrole-HTI photoswitiches<!>Prec... | <p>Visible-light activated small molecule photoswitches comprise a class of molecular machines that are the subject of a great deal of interest in fields such as drug delivery, data storage, and photomechanical polymers. 1 Seminal advances in this field were accordingly recognized with the Nobel Prize in Chemistry in 2... | ChemRxiv |
Thorium–ligand multiple bonds via reductive deprotection of a trityl group | Reaction of [Th(I)(NR 2 ) 3 ] (R ¼ SiMe 3 ) (2) with KECPh 3 (E ¼ O, S) affords the thorium chalcogenates, [Th(ECPh 3 )(NR 2 ) 3 ] (3, E ¼ O; 4, E ¼ S), in moderate yields. Reductive deprotection of the trityl group from 3 and 4 by reaction with KC 8 , in the presence of 18-crown-6, affords the thorium oxo complex, [K(... | thorium–ligand_multiple_bonds_via_reductive_deprotection_of_a_trityl_group | 5,190 | 123 | 42.195122 | Introduction<!>Results and discussion<!>View Article Online<!>Conclusions<!>Experimental<!>[Th(Cl)(NR 2 ) 3 ] (1)<!>X-ray crystallography<!>Computational details | <p>The study of actinide-ligand multiple bonds has intensied in recent years due to the need to understand the extent of both forbital participation and covalency in actinide-ligand bonding. [1][2][3][4][5][6][7][8][9] In this regard, the past ten years have seen considerable progress in the synthesis of oxo, [10][11]... | Royal Society of Chemistry (RSC) |
Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins | BackgroundAlthough it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within th... | pattern_similarity_study_of_functional_sites_in_protein_sequences:_lysozymes_and_cystatins | 6,685 | 265 | 25.226415 | Background<!>PCS classification<!><!>Segment pattern similarity search for active sites<!><!>Segment pattern similarity search for active sites<!><!>Segment pattern similarity search for active sites<!><!>HSS search for substrate binding sites<!><!>HSS search for substrate binding sites<!>Substrate binding sites report... | <p>In their recent review of protein sequence analysis in silico, Michalovich et al. [1] described the methodology for transferring functional annotation of known proteins to a novel protein. Computer-assisted technology is used to search for and assign the similarity from databases of well-maintained and previously an... | PubMed Open Access |
FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes | Human adipocytes express high levels of two distinct lipid droplet proteins, Fat Specific Protein 27 (FSP27; also called CIDEC), a member of the CIDE family, and perilipin1 (PLIN1), a member of the PAT family. Both proteins play a role in fat metabolism in adipocytes, but how they interact is not known. Our present stu... | fsp27_and_plin1_interaction_promotes_the_formation_of_large_lipid_droplets_in_human_adipocytes | 2,169 | 157 | 13.815287 | 1. Introduction<!>2.1. Materials<!>2.2. Cell culture<!>2.3. Immunostaining<!>2.4. Lentivirus production and transduction<!>2.5. Adenovirus transduction<!>2.6. Immunoprecipitation<!>2.7. Lipid droplet staining<!>2.8. Microscopy<!>2.9. Lipolysis and Triglyceride Determination<!>3.1. FSP27 co-localizes with PLIN1 in human... | <p>Cellular lipid droplets (LDs), now considered to be dynamic intracellular organelles, are composed of a core of neutral lipids surrounded by a phospholipid monolayer and associated proteins [1; 2; 3; 4; 5]. Proteins associated with the surface of LDs contribute to the biogenesis, maturation and stability of these or... | PubMed Author Manuscript |
Infrared Irradiation‐Assisted Solvent‐Free Pd‐Catalyzed (Hetero)aryl‐aryl Coupling via C−H Bond Activation | AbstractThe increasing attention towards environmentally friendly synthetic protocols has boosted studies directed to the development of green and sustainable methods for direct C−H bond arylation of (hetero)arenes. In this context, here the infrared (IR) irradiation‐assisted solvent‐free Pd‐catalyzed direct C−H bond a... | infrared_irradiation‐assisted_solvent‐free_pd‐catalyzed_(hetero)aryl‐aryl_coupling_via_c−h_bond_acti | 7,242 | 108 | 67.055556 | <!>Introduction<!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!><!>Results and Discussion<!>Conclusion<!>General rema... | <p>G. Albano, G. Decandia, M. A. M. Capozzi, N. Zappimbulso, A. Punzi, G. M. Farinola, ChemSusChem
2021, 14, 3391.</p><!><p>Green chemistry is defined as the "design of chemical products and processes to reduce or eliminate the use and generation of hazardous substances" and is based on the well‐known twelve principles... | PubMed Open Access |
Angiogenin regulates PKD activation and COX-2 expression induced by TNF-\xce\xb1 and bradykinin in the colonic myofibroblast | Introduction: The myofibroblast is a gastrointestinal stromal cell that is a target of tumor necrosis factor-alpha (TNF-\xce\xb1), a pro-inflammatory cytokine strongly implicated in colitis-associated cancer. Crosstalk between TNF-\xce\xb1 and other pro-inflammatory mediators amplify inflammatory signaling but the mech... | angiogenin_regulates_pkd_activation_and_cox-2_expression_induced_by_tnf-\xce\xb1_and_bradykinin_in_t | 2,255 | 258 | 8.74031 | Introduction<!>Materials and methods<!>Cell culture<!>Isolation of primary mouse myofibroblasts<!>Isolation of primary human myofibroblasts<!>SDS-PAGE and immunoblotting<!>ELISA<!>Materials and reagents<!>TNF-\xce\xb1 enhances bradykinin-mediated PKD phosphorylation and leads to synergistic COX-2 expression in primary ... | <p>Chronic inflammatory bowel disease (IBD) predisposes to colorectal cancer, occurring in up to 18% of patients [1]. Colitis-associated cancer is characterized by rapid progression and high mortality compared to sporadic forms [2,3], and the risk increases with the extent, duration, and severity of colitis. While the ... | PubMed Author Manuscript |
Efficient photoredox conversion of alcohol to aldehyde and H<sub>2</sub> by heterointerface engineering of bimetal–semiconductor hybrids | Controllable and precise design of bimetal-or multimetal-semiconductor nanostructures with efficient light absorption, charge separation and utilization is strongly desired for photoredox catalysis applications in solar energy conversion. Taking advantage of Au nanorods, Pt nanoparticles, and CdS as the plasmonic metal... | efficient_photoredox_conversion_of_alcohol_to_aldehyde_and_h<sub>2</sub>_by_heterointerface_engineer | 5,372 | 121 | 44.396694 | Introduction<!>Results and discussion<!>Conclusions<!>Synthesis of Au NRs<!>Preparation of Au-Pt<!>Preparation of Au-Pt@CdS<!>Material characterization<!>FDTD simulations<!>Photoactivity<!>Conflicts of interest | <p>Harvesting solar energy to drive articial photosynthesis for the production of value-added chemicals and renewable energy is a promising strategy to solve the growing worldwide energy crisis. [1][2][3][4][5] However, the solar-to-chemical conversion efficiency of semiconductors is oen limited by their nite light ... | Royal Society of Chemistry (RSC) |
Examining sterically demanding lysine analogs for histone lysine methyltransferase catalysis | Methylation of lysine residues in histone proteins is catalyzed by S-adenosylmethionine (SAM)dependent histone lysine methyltransferases (KMts), a genuinely important class of epigenetic enzymes of biomedical interest. Here we report synthetic, mass spectrometric, nMR spectroscopic and quantum mechanical/molecular mech... | examining_sterically_demanding_lysine_analogs_for_histone_lysine_methyltransferase_catalysis | 4,822 | 442 | 10.909502 | <!>Results and Discussion<!>conclusion | <p>its main chain also plays an important role in productive KMT catalysis 20 . Despite these recent findings that shed light on basic understanding of KMT catalysis, a broader scope of lysine analogs as substrates for KMTs has not been explored yet. Here we report enzymatic evaluations of sterically demanding lysine a... | Scientific Reports - Nature |
PPAR\xce\xb1 activation inhibits endothelin-1-induced cardiomyocyte hypertrophy by prevention of NFATc4 binding to GATA-4 | Peroxisome proliferator-activated receptor alpha (PPAR\xce\xb1) has been implicated in the pathogenesis of cardiac hypertrophy, although its mechanism of action remains largely unknown. To determine the effect of PPAR\xce\xb1 activation on endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and explore its molecular ... | ppar\xce\xb1_activation_inhibits_endothelin-1-induced_cardiomyocyte_hypertrophy_by_prevention_of_nfa | 2,610 | 192 | 13.59375 | Introduction<!>Chemicals and antibodies<!>Primary culture and studies of rat cardiomyocytes<!>Immunoprecipitation and Western blotting<!>Electrophoretic mobility shift assay<!>RNA isolation and quantitative RT-PCR<!>Microscopic evaluation<!>Statistical analysis<!>Activated PPAR\xce\xb1 co-IP of NFATc4 from nuclei of ca... | <p>Cardiac hypertrophy is thought to be an adaptive response of the heart to preserve pump function under adverse conditions, and prolonged hypertrophy is a major predictor of arrhythmias and sudden death or heart failure [1–4]. Evidence is increasing that endothelin-1 (ET-1)1, a 21-amino acid peptide, contributes to t... | PubMed Author Manuscript |
Vibrational Probes of Molybdenum Cofactor\xe2\x80\x93Protein Interactions in Xanthine Dehydrogenase | The pyranopterin dithiolene (PDT) ligand is an integral component of the molybdenum cofactor (Moco) found in all molybdoenzymes with the sole exception of nitrogenase. However, the roles of the PDT in catalysis are still unknown. The PDT is believed to be bound to the proteins by an extensive hydrogen bonding network, ... | vibrational_probes_of_molybdenum_cofactor\xe2\x80\x93protein_interactions_in_xanthine_dehydrogenase | 4,135 | 294 | 14.064626 | INTRODUCTION<!>Enzyme Preparation and Characterization.<!>Preparation of the XDH Enzyme-Product Complexes.<!>Electronic Absorption Spectroscopy.<!>Resonance Raman Spectroscopy.<!>Computational Details.<!>Electronic Absorption Spectroscopy.<!>Resonance Raman Spectroscopy.<!>Rapid reaction kinetics of XDH variants.<!>CON... | <p>R. capsulatus xanthine dehydrogenase (RcXDH) is a pyranopterin molybdenum enzyme1–3 that possesses broad substrate specificity1, 3–4 and a high degree of sequence homology with the mammalian molybdenum hydroxylase, xanthine oxidoreductase (XOR). XDH and XOR belong to the xanthine oxidase (XO) family of pyranopterin ... | PubMed Author Manuscript |
Isolated Neutral [4]Helicene Radical Provides Insight into Consecutive Two-Photon Excitation Photocatalysis | Direct activation of strong bonds in readily available, benchtop substrates offer a straightforward simplification, albeit in most cases existing catalytic systems are limited to unlock such activation. In recent years, a surge of in-situ generated organic radicals that can act as potent photoinduced electron transfer ... | isolated_neutral_[4]helicene_radical_provides_insight_into_consecutive_two-photon_excitation_photoca | 5,053 | 251 | 20.131474 | INTRODUCTION<!>RESULTS AND DISCUSSION<!>Photocatalytic dehalogenation of aryl halides.<!>Table 1: Substrate scope for the photoredox reductive dehalogenation of aryl halides enabled by neutral helicene radical.<!>Table 2: Scope for the reductive functionalization of aryl halides under photoredox condition catalyzed by ... | <p>Over the past decade, photoredox catalysis has received a fast and growing interest from the world of synthetic chemistry. 1 By combining visible light with a photocatalyst (PC), a large variety of efficient and selective transformations have been achieved under mild conditions, during which the excited state PC is ... | ChemRxiv |
Preparation of different thin film catalysts by direct current magnetron sputtering for hydrogen generation | In this study, thin films of Co, Ni, Pd, and Pt were prepared on Co 3 O 4 support material in pellet form using the direct current (DC) magnetron sputtering method for use as catalysts for hydrogen generation from NaBH 4 .Characterization of the catalysts was carried out using X-ray diffraction (XRD), scanning electron... | preparation_of_different_thin_film_catalysts_by_direct_current_magnetron_sputtering_for_hydrogen_gen | 2,369 | 151 | 15.688742 | 1. Introduction<!>2.1. Synthesis of support material<!>2.2. Catalyst preparation with coating deposition<!><!>2.3. Characterization<!>2.4. Measurement of hydrogen generation rate<!>3.1. Characterization of the catalysts<!><!>3.1. Characterization of the catalysts<!><!>3.1. Characterization of the catalysts<!><!>3.1. Ch... | <p>The reduction of greenhouse gas emissions worldwide and the use of alternative fuels in transportation have become a forced option. According to recent research, hydrogen is an innovative fuel option for the automotive field and could replace conventional petroleum-derived liquid mixtures in passenger cars over time... | PubMed Open Access |
Comparative Studies of Mammalian Acid Lipases: Evidence for a New Gene Family in Mouse and Rat (Lipo) | At least six families of mammalian acid lipases (E.C. 3.1.1.-) catalyse the hydrolysis of triglycerides in the body, designated as LIPA (lysosomal), LIPF (gastric), LIPJ (testis) and LIPK, LIPM and LIPN (epidermal), which belong to the AB hydrolase superfamily. In this study, in silico methods were used to predict the ... | comparative_studies_of_mammalian_acid_lipases:_evidence_for_a_new_gene_family_in_mouse_and_rat_(lipo | 3,412 | 265 | 12.875472 | Introduction<!>In silico mammalian acid lipase gene and protein identification<!>Predicted Structures and Properties of Mouse Acid Lipases<!>Mouse Acid Lipase Gene Expression<!>Phylogenetic Studies and Sequence Divergence<!>Alignments of Mouse Acid Lipase Amino Acid Sequences<!>Predicted Secondary and Tertiary Structur... | <p>At least six mammalian acid lipase genes have been reported, including LIPA, encoding lysosomal acid lipase/cholesteryl ester hydrolase (E.C.3.1.1.13) (Anderson & Sando, 1991; Anderson et al., 1994; Ameis et al, 1994); LIPF, encoding a gastric lipase (E.C.3.1.1.3) (Bodmer et al., 1987; Lohse et al., 1997) ; LIPJ, ex... | PubMed Author Manuscript |
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