abstract：:Drug resistance continues to be a growing global problem. The efficacy of small molecule inhibitors is threatened by pools of genetic diversity in all systems, including antibacterials, antifungals, cancer therapeutics, and antivirals. Resistant variants often include combinations of active site mutations and distal "...

journal_title：ACS chemical biology

authors： Henes M,Lockbaum GJ,Kosovrasti K,Leidner F,Nachum GS,Nalivaika EA,Lee SK,Spielvogel E,Zhou S,Swanstrom R,Bolon DNA,Kurt Yilmaz N,Schiffer CA

更新日期：2019-11-15 00:00:00

abstract：:SGK3 is a PX domain containing protein kinase activated at endosomes downstream of class 1 and 3 PI3K family members by growth factors and oncogenic mutations. SGK3 plays a key role in mediating resistance of breast cancer cells to class 1 PI3K or Akt inhibitors, by substituting for the loss of Akt activity and restor...

journal_title：ACS chemical biology

authors： Tovell H,Testa A,Zhou H,Shpiro N,Crafter C,Ciulli A,Alessi DR

更新日期：2019-09-20 00:00:00

abstract：:Nonribosomal peptides are important natural products biosynthesized by nonribosomal peptide synthetases (NRPSs). Adenylation (A) domains of NRPSs are highly specific for the substrate they recognize. This recognition is determined by 10 residues in the substrate-binding pocket, termed the specificity code. This findin...

journal_title：ACS chemical biology

authors： Throckmorton K,Vinnik V,Chowdhury R,Cook T,Chevrette MG,Maranas C,Pfleger B,Thomas MG

更新日期：2019-09-20 00:00:00

abstract：:Photo- or optoacoustics (OA) imaging is increasingly being used as a non-invasive imaging method that can simultaneously reveal structure and function in deep tissue. However, the most frequent transgenic OA labels are current fluorescent proteins that are not optimized for OA imaging. Thus, they lack OA signal streng...

journal_title：ACS chemical biology

authors： Fuenzalida Werner JP,Mishra K,Huang Y,Vetschera P,Glasl S,Chmyrov A,Richter K,Ntziachristos V,Stiel AC

更新日期：2019-09-20 00:00:00

abstract：:WS9326A and annimycin are produced by Streptomyces asterosporus DSM 41452. WS9326A is a nonribosomal peptide synthetase-(NRPS-) derived depsipeptide containing a cinnamoyl moiety, while annimycin is a linear polyketide bearing a 2-amino-3-hydroxycyclopent-2-enone (C5N) group. Both gene clusters have been sequenced and...

journal_title：ACS chemical biology

authors： Zhu J,Zhang S,Zechel DL,Paululat T,Bechthold A

更新日期：2019-08-16 00:00:00

abstract：:Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...

journal_title：ACS chemical biology

authors： Mannella V,Quilici G,Nigro EA,Lampis M,Minici C,Degano M,Boletta A,Musco G

更新日期：2019-08-16 00:00:00

abstract：:Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in h...

journal_title：ACS chemical biology

authors： Barr D,Szennyes E,Bokor É,Al-Oanzi ZH,Moffatt C,Kun S,Docsa T,Sipos Á,Davies MP,Mathomes RT,Snape TJ,Agius L,Somsák L,Hayes JM

更新日期：2019-07-19 00:00:00

abstract：:Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression...

journal_title：ACS chemical biology

authors： Dehm D,Krumbholz J,Baunach M,Wiebach V,Hinrichs K,Guljamow A,Tabuchi T,Jenke-Kodama H,Süssmuth RD,Dittmann E

更新日期：2019-06-21 00:00:00

abstract：:Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread application and development as a drug. Here, we report the identification of Streptomyces sp. S816, isolated from Philippine man...

journal_title：ACS chemical biology

authors： Zhou S,Song L,Masschelein J,Sumang FAM,Papa IA,Zulaybar TO,Custodio AB,Zabala D,Alcantara EP,de Los Santos ELC,Challis GL

更新日期：2019-06-21 00:00:00

abstract：:New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of R...

journal_title：ACS chemical biology

authors： Kudo K,Koiwai H,Kagaya N,Nishiyama M,Kuzuyama T,Shin-Ya K,Ikeda H

更新日期：2019-06-21 00:00:00

abstract：:Small molecules that bind to voltage-gated sodium channels (VGSCs) are promising leads in the treatment of numerous neurodegenerative diseases and pain. Nature is a highly skilled medicinal chemist in this regard, designing potent VGSC ligands capable of binding to and blocking the channel, thereby offering compounds ...

journal_title：ACS chemical biology

authors： Lukowski AL,Denomme N,Hinze ME,Hall S,Isom LL,Narayan ARH

更新日期：2019-05-17 00:00:00

abstract：:Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measuremen...

journal_title：ACS chemical biology

authors： Levina A,Lay PA

更新日期：2019-05-17 00:00:00

abstract：:Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significan...

journal_title：ACS chemical biology

authors： Moon K,Xu F,Zhang C,Seyedsayamdost MR

更新日期：2019-04-19 00:00:00

abstract：:STAT family proteins are important mediators of cell signaling and represent therapeutic targets for the treatment of human diseases. Most STAT inhibitors target the protein-protein interaction domain, the SH2 domain, but specificity for a single STAT protein is often limited. Recently, we developed catechol bisphosph...

journal_title：ACS chemical biology

authors： Gräb J,Berg A,Blechschmidt L,Klüver B,Rubner S,Fu DY,Meiler J,Gräber M,Berg T

更新日期：2019-04-19 00:00:00

abstract：:Stapled peptides have great potential as modulators of protein-protein interactions (PPIs). However, there is a vast landscape of chemical features that can be varied for any given peptide, and identifying a set of features that maximizes cellular uptake and subsequent target engagement remains a key challenge. Herein...

journal_title：ACS chemical biology

authors： Wu Y,Kaur A,Fowler E,Wiedmann MM,Young R,Galloway WRJD,Olsen L,Sore HF,Chattopadhyay A,Kwan TT,Xu W,Walsh SJ,de Andrade P,Janecek M,Arumugam S,Itzhaki LS,Lau YH,Spring DR

更新日期：2019-03-15 00:00:00

abstract：:To combat the increasing spread of antimicrobial resistance and the shortage of novel anti-infectives, one strategy for the development of new antibiotics is to optimize known chemical scaffolds. Here, we focus on the biosynthetic engineering of Amycolatopsis sulphurea for derivatization of the atypical tetracycline c...

journal_title：ACS chemical biology

authors： Lukežič T,Fayad AA,Bader C,Harmrolfs K,Bartuli J,Groß S,Lešnik U,Hennessen F,Herrmann J,Pikl Š,Petković H,Müller R

更新日期：2019-03-15 00:00:00

abstract：:Nearly one-third of the encoded proteome is comprised of secretory proteins that enable communication between cells and organ systems, playing a ubiquitous role in human health and disease. High-throughput detection of secreted proteins would enhance efforts to identify therapies for secretion-related diseases. Using ...

journal_title：ACS chemical biology

authors： Iannotti MJ,MacArthur R,Jones R,Tao D,Singeç I,Michael S,Inglese J

更新日期：2019-03-15 00:00:00

abstract：:Leishmaniases affect the poorest people on earth and have no effective drug therapy. Here, we present the crystal structure of the mitochondrial isoform of class I fumarate hydratase (FH) from Leishmania major and compare it to the previously determined cytosolic Leishmania major isoform. We further describe the mecha...

journal_title：ACS chemical biology

authors： Feliciano PR,Drennan CL,Nonato MC

更新日期：2019-02-15 00:00:00

abstract：:Despite the stereospecificity of translation for l-amino acids (l-AAs) in vivo, synthetic biologists have enabled ribosomal incorporation of d-AAs in vitro toward encoding polypeptides with pharmacologically desirable properties. However, the steps in translation limiting d-AA incorporation need clarification. In this...

journal_title：ACS chemical biology

authors： Liljeruhm J,Wang J,Kwiatkowski M,Sabari S,Forster AC

更新日期：2019-02-15 00:00:00

abstract：:Hydrogen sulfide (H2S) is an important gasotransmitter and biomolecule, and many synthetic small-molecule H2S donors have been developed for H2S-related research. One important class of triggerable H2S donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly conver...

journal_title：ACS chemical biology

authors： Levinn CM,Steiger AK,Pluth MD

更新日期：2019-02-15 00:00:00

abstract：:RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor pro...

journal_title：ACS chemical biology

authors： Assimon VA,Tang Y,Vargas JD,Lee GJ,Wu ZY,Lou K,Yao B,Menon MK,Pios A,Perez KC,Madriaga A,Buchowiecki PK,Rolfe M,Shawver L,Jiao X,Le Moigne R,Zhou HJ,Anderson DJ

更新日期：2019-02-15 00:00:00

abstract：:Botulinum neurotoxins (BoNTs) are the most potent toxins known to man and a significant threat as weapons of bioterrorism. BoNTs contain a metalloprotease domain that blocks neurotransmitter release in nerve terminals, resulting in a descending, flaccid paralysis with a 5-10% mortality rate. Existing treatment options...

journal_title：ACS chemical biology

authors： Garland M,Babin BM,Miyashita SI,Loscher S,Shen Y,Dong M,Bogyo M

更新日期：2019-01-18 00:00:00

abstract：:O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function. Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells. Here, we develop...

journal_title：ACS chemical biology

authors： Li J,Li Z,Duan X,Qin K,Dang L,Sun S,Cai L,Hsieh-Wilson LC,Wu L,Yi W

更新日期：2019-01-18 00:00:00

abstract：:A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...

journal_title：ACS chemical biology

authors： Sharma A,Toy W,Guillen VS,Sharma N,Min J,Carlson KE,Mayne CG,Lin S,Sabio M,Greene G,Katzenellenbogen BS,Chandarlapaty S,Katzenellenbogen JA

更新日期：2018-12-21 00:00:00

abstract：:Miniproteins have a size between that of larger biologics and small molecules and presumably possess the advantages of both; they represent an expanding class of promising scaffolds for the design of affinity reagents, enzymes, and therapeutics. Conventional strategies to promote cellular uptake of miniproteins rely o...

journal_title：ACS chemical biology

authors： Meng X,Li T,Zhao Y,Wu C

更新日期：2018-11-16 00:00:00

abstract：:The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...

journal_title：ACS chemical biology

authors： Cullen A,D'Agostino PM,Mazmouz R,Pickford R,Wood S,Neilan BA

更新日期：2018-11-16 00:00:00

abstract：:Allosteric inhibitors can be more difficult to optimize without an understanding of how their binding influences the conformational motions of the target. Here, we used an integrated computational and experimental approach to probe the molecular mechanism of an allosteric inhibitor of heat shock protein 70 (Hsp70). Th...

journal_title：ACS chemical biology

authors： Rinaldi S,Assimon VA,Young ZT,Morra G,Shao H,Taylor IR,Gestwicki JE,Colombo G

更新日期：2018-11-16 00:00:00

abstract：:New machine learning methods to analyze raw chemical and biological data are now widely accessible as open-source toolkits. This positions researchers to leverage powerful, predictive models in their own domains. We caution, however, that the application of machine learning to experimental research merits careful cons...

journal_title：ACS chemical biology

authors： Chuang KV,Keiser MJ

更新日期：2018-10-19 00:00:00

abstract：:A Natural Compound Library containing myxobacterial secondary metabolites was screened in murine macrophages for novel activators of IL-1β maturation and secretion. The most potent of three hits in total was a so far undescribed metabolite, which was identified from the myxobacterium Hyalangium minutum strain Hym3. Wh...

journal_title：ACS chemical biology

authors： Surup F,Chauhan D,Niggemann J,Bartok E,Herrmann J,Keck M,Zander W,Stadler M,Hornung V,Müller R

更新日期：2018-10-19 00:00:00

abstract：:Matrix metalloproteases (MMPs) are a large family of zinc-dependent endopeptidases involved in a diverse set of physiological and pathological processes, most notably in cancer. Current methods for imaging and quantifying MMP activity lack sufficient selectivity and spatiotemporal resolution to allow studies of specif...

journal_title：ACS chemical biology

authors： Amara N,Tholen M,Bogyo M

更新日期：2018-09-21 00:00:00

abstract：:Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug target, we sought examples of topologically unrelated ligands that ...

journal_title：ACS chemical biology

authors： Pottel J,Levit A,Korczynska M,Fischer M,Shoichet BK

更新日期：2018-09-21 00:00:00

abstract：:Access to well-defined ubiquitin conjugates has been key to elucidating the biochemical functions of proteins in the ubiquitin signaling network. Yet, we have a poor understanding of how deubiquitinases and ubiquitin-binding proteins respond to ubiquitin modifications when anchored to a protein other than ubiquitin or...

journal_title：ACS chemical biology

authors： Chang LH,Strieter ER

更新日期：2018-09-21 00:00:00

abstract：:Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously b...

journal_title：ACS chemical biology

authors： Vitvitsky V,Miljkovic JL,Bostelaar T,Adhikari B,Yadav PK,Steiger AK,Torregrossa R,Pluth MD,Whiteman M,Banerjee R,Filipovic MR

更新日期：2018-08-17 00:00:00

abstract：:Reactive oxygen species (ROS) play an important role in the onset of Parkinson's disease (PD), and deciphering protective mechanisms is a major goal for therapeutic development. Here, DJ-1 (PARK7) gained major attention when a conserved cysteine residue with a putative role in oxidative stress sensing/protection was l...

journal_title：ACS chemical biology

authors： Drechsel J,Mandl FA,Sieber SA

更新日期：2018-08-17 00:00:00

abstract：:Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cel...

journal_title：ACS chemical biology

authors： Libby CJ,Zhang S,Benavides GA,Scott SE,Li Y,Redmann M,Tran AN,Otamias A,Darley-Usmar V,Napierala M,Zhang J,Augelli-Szafran CE,Zhang W,Hjelmeland AB

更新日期：2018-08-17 00:00:00

abstract：:Vitamin A serves essential functions in mammalian biology as a signaling molecule and chromophore. This lipid can be synthesized from more than 50 putative dietary provitamin A precursor molecules which contain at least one unsubstituted β-ionone ring. We here scrutinized the enzymatic properties and substrate specifi...

journal_title：ACS chemical biology

authors： Kelly ME,Ramkumar S,Sun W,Colon Ortiz C,Kiser PD,Golczak M,von Lintig J

更新日期：2018-08-17 00:00:00

abstract：:Benzodiazepines are clinically relevant drugs that bind to GABAA neurotransmitter receptors at the α+/γ2- interfaces and thereby enhance GABA-induced chloride ion flux leading to neuronal hyperpolarization. However, the structural basis of benzodiazepine interactions with their high-affinity site at GABAA receptors is...

journal_title：ACS chemical biology

authors： Elgarf AA,Siebert DCB,Steudle F,Draxler A,Li G,Huang S,Cook JM,Ernst M,Scholze P

更新日期：2018-08-17 00:00:00

abstract：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

journal_title：ACS chemical biology

authors： Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

更新日期：2018-08-17 00:00:00

abstract：:Chemical genetics is a powerful approach for identifying therapeutically active small molecules, but identifying the mechanisms of action underlying hit compounds remains challenging. Chemoproteomic platforms have arisen to tackle this challenge and enable rapid mechanistic deconvolution of small-molecule screening hi...

journal_title：ACS chemical biology

authors： Counihan JL,Wiggenhorn AL,Anderson KE,Nomura DK

更新日期：2018-08-17 00:00:00

abstract：:The anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic effects of benzodiazepine site ligands are mainly elicited by allosteric modulation of GABAA receptors via their extracellular αx+/γ2- ( x = 1, 2, 3, 5) interfaces. In addition, a low affinity binding site at the homologous α+/β- interfaces was rep...

journal_title：ACS chemical biology

authors： Siebert DCB,Bampali K,Puthenkalam R,Varagic Z,Sarto-Jackson I,Scholze P,Sieghart W,Mihovilovic MD,Schnürch M,Ernst M

更新日期：2018-08-17 00:00:00