解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::The epidermal growth-factor-like domain A (EGF-A) of the low-density lipoprotein (LDL) receptor is a promising lead for therapeutic inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the clinical potential of EGF-A is limited by its suboptimal affinity for PCSK9. Here, we use phage display t...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00991
更新日期:2021-01-29 00:00:00
abstract::Current therapeutic interventions for both heart disease and heart failure are largely insufficient and associated with undesired side effects. Biomedical research has emphasized the role of sarcomeric protein function for the normal performance and energy efficiency of the heart, suggesting that directly targeting th...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00908
更新日期:2021-01-15 00:00:00
abstract::Siderophores are iron-chelating molecules produced by microorganisms and plants to acquire exogenous iron. Siderophore biosynthetic enzymology often produces elaborate and unique molecules through unusual reactions to enable specific recognition by the producing organisms. Herein, we report the structure of two sidero...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00809
更新日期:2021-01-15 00:00:00
abstract::A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00888
更新日期:2021-01-15 00:00:00
abstract::The emergence of multidrug-resistant Staphylococcus aureus strains has become a serious clinical problem. Iron is absolutely required for the bacterial growth, virulence associated with colonization, and survival from the host immune system. The FeoB protein is a major iron permease in bacterial ferrous iron transport...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00842
更新日期:2021-01-15 00:00:00
abstract::mRNA-based therapies and vaccines constitute a disruptive technology with the potential to revolutionize modern medicine. Chemically modified 5' cap structures have provided access to mRNAs with superior translational properties that could benefit the currently flourishing mRNA field. Prime examples of compounds that ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00864
更新日期:2021-01-13 00:00:00
abstract::Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The current treatment options for AD are limited to ameliorating cognitive decline temporarily and not reversing or preventing the progression of dementia. Hence, more effective therapeutic strategies are needed ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00851
更新日期:2020-12-18 00:00:00
abstract::Lipopolysaccharide (LPS) is a crucial component in the outer membrane of Gram-negative bacteria that contributes to both pathogenicity as well as immunity against pathogenic bacteria. Typical LPS contains GlcN disaccharide as the core of lipid A. However, some bacteria such as Acidithiobacillus ferrooxidans and Leptos...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00791
更新日期:2020-12-18 00:00:00
abstract::Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Ther...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00700
更新日期:2020-11-20 00:00:00
abstract::Bacterial resistance to conventional antibiotics is of major concern. Antimicrobial peptides (AMPs) are considered excellent alternatives. Among them, D-cateslytin (D-Ctl, derivative of a host defense peptide) has shown high efficiency against a broad spectrum of bacteria. The first target of AMPs is the outer membran...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00622
更新日期:2020-10-16 00:00:00
abstract::Light-activated protein domains provide a convenient, modular, and genetically encodable sensor for optogenetics and optobiology. Although these domains have now been deployed in numerous systems, the precise mechanism of photoactivation and the accompanying structural dynamics that modulate output domain activity rem...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00543
更新日期:2020-10-16 00:00:00
abstract::Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00645
更新日期:2020-10-16 00:00:00
abstract::Cell-penetrating peptides (CPPs) are capable of delivering membrane-impermeable cargoes (including small molecules, peptides, proteins, nucleic acids, and nanoparticles) into the cytosol of mammalian cells and have the potential to revolutionize biomedical research and drug discovery. However, the mechanism of action ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00478
更新日期:2020-09-18 00:00:00
abstract::The ever-growing drug resistance problem worldwide highlights the urgency to discover and develop new drugs. Microbial natural products are a prolific source of drugs. Genome sequencing has revealed a tremendous amount of uncharacterized natural product biosynthetic gene clusters (BGCs) encoded within microbial genome...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00581
更新日期:2020-09-18 00:00:00
abstract::Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthe...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00564
更新日期:2020-09-18 00:00:00
abstract::Microbes are essential to the global ecosystem, but undesirable microbial growth causes issues ranging from food spoilage and infectious diseases to harmful cyanobacterial blooms. The use of chemicals to control microbial growth has achieved significant success, while specific roles for a majority of essential genes i...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00507
更新日期:2020-08-21 00:00:00
abstract::Pyrrole-imidazole alkaloids are natural products isolated from marine sponges, holobiont metazoans that are associated with symbiotic microbiomes. Pyrrole-imidazole alkaloids have attracted attention due to their chemical complexity and their favorable pharmacological properties. However, insights into how these molec...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00375
更新日期:2020-08-21 00:00:00
abstract::Signal transducer and activator of transcription (STAT) proteins have important biological functions; however, deregulation of STAT signaling is a driving force behind the onset and progression of inflammatory diseases and cancer. While their biological roles suggest that STAT proteins would be valuable targets for de...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00046
更新日期:2020-07-17 00:00:00
abstract::Small molecule kinase inhibitors that stabilize distinct ATP binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhi...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00429
更新日期:2020-07-17 00:00:00
abstract::The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00982
更新日期:2020-07-17 00:00:00
abstract::RNA modifications play important roles in RNA structures and regulation of gene expression and translation. We report the first RNA modification on the phosphate, the RNA phosphorothioate (PS) modification, discovered in both prokaryotes and eukaryotes. The PS modification is also first reported on nucleic acids of eu...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00163
更新日期:2020-06-19 00:00:00
abstract::Terpene synthases (TS) are classified into two broad types, Class I and II, based on the chemical strategy for initial carbocation formation and motif sequences of the catalytic site. We have recently identified a new class of enzymes, Class IB, showing the acceptability of long (C20-C35) prenyl-diphosphates as substr...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00145
更新日期:2020-06-19 00:00:00
abstract::Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00031
更新日期:2020-06-19 00:00:00
abstract::A biophysical understanding of the mechanistic, chemical, and physical origins underlying antibiotic action and resistance is vital to the discovery of novel therapeutics and the development of strategies to combat the growing emergence of antibiotic resistance. The site-specific introduction of stable-isotope labels ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b01054
更新日期:2020-05-15 00:00:00
abstract::The heterologous biosynthesis of complex natural products has enabled access to polyketide, nonribosomal peptide, isoprenoid, and other compounds with wide-spanning societal value. Though several surrogate host systems exist, Escherichia coli is often a preferred choice due to its rapid growth kinetics and extensive m...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00827
更新日期:2020-05-15 00:00:00
abstract::3-Oxo-β-sultams are four-membered ring ambident electrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-β-sultam inhibitors ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00090
更新日期:2020-04-17 00:00:00
abstract::BRD4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00058
更新日期:2020-04-17 00:00:00
abstract::Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermo...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00895
更新日期:2020-03-20 00:00:00
abstract::Rediscovery of known compounds and time consumed in identification, especially high molecular weight compounds with complex structure, have let down interest in drug discovery. In this study, whole-genome analysis of microbe and Global Natural Products Social (GNPS) molecular networking helped in initial understanding...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00026
更新日期:2020-03-20 00:00:00
abstract::The endoplasmic reticulum (ER) is the initial site of biogenesis of secretory pathway proteins, including proteins localized to the ER, Golgi, lysosomes, intracellular vesicles, plasma membrane, and extracellular compartments. Proteins within the secretory pathway contain a high abundance of disulfide bonds to protect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b01014
更新日期:2020-02-21 00:00:00
abstract::Ca(II) ions are critical for the proper function of neurons by contributing to synaptic signaling and regulating neuronal plasticity. Dysregulation of Ca(II) is associated with a number of pathologies that cause neurodegeneration; therefore the ability to monitor Ca(II) intracellularly is an important target for molec...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00638
更新日期:2020-02-21 00:00:00
abstract::Histone post-translational modifications (PTMs) are crucial for many cellular processes including mitosis, transcription, and DNA repair. The cellular readout of histone PTMs is dependent on both the chemical modification and histone site, and the array of histone PTMs on chromatin is dynamic throughout the eukaryotic...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00651
更新日期:2020-01-17 00:00:00
abstract::Epitranscriptomic modifications play an important role in RNA function and can impact gene expression. Here, we apply a chemical proteomics approach to investigate readers of N1-methyladenosine (m1A), a poorly characterized modification on mammalian mRNA. We find that YTHDF proteins, known m6A readers, recognize m1A-m...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00655
更新日期:2020-01-17 00:00:00
abstract::Ineffective cellular delivery is a common problem in numerous biological applications. Developing delivery reagents that work robustly in a variety of experimental settings remains a challenge. Herein, we report how peptides derived from the prototypical cell penetrating peptide TAT can be used in combination with a s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00585
更新日期:2019-12-20 00:00:00
abstract::FAT10 is a ubiquitin-like protein suggested to target proteins for proteasomal degradation. It is highly upregulated upon pro-inflammatory cytokines, namely, TNFα, IFNγ, and IL6, and was found to be highly expressed in various epithelial cancers. Evidence suggests that FAT10 is involved in cancer development and may h...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00667
更新日期:2019-12-20 00:00:00
abstract::Regorafenib (Stivarga) is an oral small molecule kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from the reactivation of t...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00663
更新日期:2019-12-20 00:00:00
abstract::For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino acids Phe353, Ile418, Met419, and Ile593 ("triad determinants") is important, and mutagenesis of these residues altered the reaction specificity of these enzymes. Here we expressed wild-type human ALOX5 and its F359W/A424I/N425M/A6...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00674
更新日期:2019-12-20 00:00:00
abstract::Drug optimization is guided by biophysical methods with increasing popularity. In the context of lead structure modifications, the introduction of methyl groups is a simple but potentially powerful approach. Hence, it is crucial to systematically investigate the influence of ligand methylation on biophysical character...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00476
更新日期:2019-12-20 00:00:00
abstract::The human ClpP proteolytic complex (HsClpP) is a serine protease located in the mitochondrial matrix and participates in the maintenance of the mitochondrial proteome among other cellular functions. HsClpP typically forms a multimeric complex with the AAA+ protein unfoldase HsClpX. Notably, compared to that of normal,...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/acschembio.9b00347
更新日期:2019-11-15 00:00:00
abstract::Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in a...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00518
更新日期:2019-11-15 00:00:00