abstract：:Numerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-π bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited ...

journal_title：ACS chemical biology

authors： Shah MB,Liu J,Zhang Q,Stout CD,Halpert JR

更新日期：2017-05-19 00:00:00

abstract：:Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a cell impermeable far-red fluorophore-tagged Hsp90 inhibitor to t...

journal_title：ACS chemical biology

authors： Crowe LB,Hughes PF,Alcorta DA,Osada T,Smith AP,Totzke J,Loiselle DR,Lutz ID,Gargesha M,Roy D,Roques J,Darr D,Lyerly HK,Spector NL,Haystead TAJ

更新日期：2017-04-21 00:00:00

abstract：:Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and str...

journal_title：ACS chemical biology

authors： Hao D,Xiao W,Liu R,Kumar P,Li Y,Zhou P,Guo F,Farmer DL,Lam KS,Wang F,Wang A

更新日期：2017-04-21 00:00:00

abstract：:The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...

journal_title：ACS chemical biology

authors： Nett RS,Contreras T,Peters RJ

更新日期：2017-04-21 00:00:00

abstract：:Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical l...

journal_title：ACS chemical biology

authors： Ranganathan A,Heine P,Rudling A,Plückthun A,Kummer L,Carlsson J

更新日期：2017-03-17 00:00:00

abstract：:N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is...

journal_title：ACS chemical biology

authors： Kutchukian PS,Warren L,Magliaro BC,Amoss A,Cassaday JA,O'Donnell G,Squadroni B,Zuck P,Pascarella D,Culberson JC,Cooke AJ,Hurzy D,Schlegel KS,Thomson F,Johnson EN,Uebele VN,Hermes JD,Parmentier-Batteur S,Finley M

更新日期：2017-02-17 00:00:00

abstract：:There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug ...

journal_title：ACS chemical biology

authors： Arencibia JM,Fröhner W,Krupa M,Pastor-Flores D,Merker P,Oellerich T,Neimanis S,Schmithals C,Köberle V,Süß E,Zeuzem S,Stark H,Piiper A,Odadzic D,Schulze JO,Biondi RM

更新日期：2017-02-17 00:00:00

abstract：:C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C-C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates cat...

journal_title：ACS chemical biology

authors： Sadler JC,Chung CH,Mosley JE,Burley GA,Humphreys LD

更新日期：2017-02-17 00:00:00

abstract：:Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involv...

journal_title：ACS chemical biology

authors： Cramer J,Krimmer SG,Fridh V,Wulsdorf T,Karlsson R,Heine A,Klebe G

更新日期：2017-01-20 00:00:00

abstract：:The canonical NF-κB signaling pathway is a mediator of the cellular inflammatory response and a target for developing therapeutics for multiple human diseases. The furthest downstream proteins in the pathway, the p50/p65 transcription factor heterodimer, have been recalcitrant toward small molecule inhibition despite ...

journal_title：ACS chemical biology

authors： Widen JC,Kempema AM,Villalta PW,Harki DA

更新日期：2017-01-20 00:00:00

abstract：:The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical pro...

journal_title：ACS chemical biology

authors： Heinzlmeir S,Kudlinzki D,Sreeramulu S,Klaeger S,Gande SL,Linhard V,Wilhelm M,Qiao H,Helm D,Ruprecht B,Saxena K,Médard G,Schwalbe H,Kuster B

更新日期：2016-12-16 00:00:00

abstract：:Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epig...

journal_title：ACS chemical biology

authors： Maurer S,Giess M,Koch O,Summerer D

更新日期：2016-12-16 00:00:00

abstract：:Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling ide...

journal_title：ACS chemical biology

authors： Ward JA,McLellan L,Stockley M,Gibson KR,Whitlock GA,Knights C,Harrigan JA,Jacq X,Tate EW

更新日期：2016-12-16 00:00:00

abstract：:Phosphatases play key roles in normal physiology and diseases. Studying phosphatases has been both essential and challenging, and the application of conventional genetic and biochemical methods has led to crucial but still limited understanding of their mechanisms, substrates, and exclusive functions within highly int...

journal_title：ACS chemical biology

authors： Fahs S,Lujan P,Köhn M

更新日期：2016-11-18 00:00:00

abstract：:Lipids are emerging as key regulators of fundamental cellular processes including cell survival, division, and death. Apoptosis, a form of programmed cell death, is accompanied by numerous membrane-related phenotypic changes. However, we have an incomplete understanding of the involvement of specific lipid structures ...

journal_title：ACS chemical biology

authors： Li N,Lizardo DY,Atilla-Gokcumen GE

更新日期：2016-09-16 00:00:00

abstract：:Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-in...

journal_title：ACS chemical biology

authors： Bauer MR,Jones RN,Baud MG,Wilcken R,Boeckler FM,Fersht AR,Joerger AC,Spencer J

更新日期：2016-08-19 00:00:00

abstract：:Aldehydes are key intermediates in many cellular processes, from endogenous metabolic pathways like glycolysis to undesired exogenously induced processes such as lipid peroxidation and DNA interstrand cross-linking. Alkyl aldehydes are well documented to be cytotoxic, affecting the functions of DNA and protein, and th...

journal_title：ACS chemical biology

authors： Yuen LH,Saxena NS,Park HS,Weinberg K,Kool ET

更新日期：2016-08-19 00:00:00

abstract：:Acute and specific sensing of diatomic gas molecules is an essential facet of biological signaling. Heme nitric oxide/oxygen binding (H-NOX) proteins are a family of gas sensors found in diverse classes of bacteria and eukaryotes. The most commonly characterized bacterial H-NOX domains are from facultative anaerobes a...

journal_title：ACS chemical biology

authors： Hespen CW,Bruegger JJ,Phillips-Piro CM,Marletta MA

更新日期：2016-08-19 00:00:00

abstract：:Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene ex...

journal_title：ACS chemical biology

authors： Deochand DK,Meariman JK,Grove A

更新日期：2016-07-15 00:00:00

abstract：:Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

journal_title：ACS chemical biology

authors： Mondal S,Rakshit A,Pal S,Datta A

更新日期：2016-07-15 00:00:00

abstract：:Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceram...

journal_title：ACS chemical biology

authors： Charoenwattanasatien R,Pengthaisong S,Breen I,Mutoh R,Sansenya S,Hua Y,Tankrathok A,Wu L,Songsiriritthigul C,Tanaka H,Williams SJ,Davies GJ,Kurisu G,Cairns JR

更新日期：2016-07-15 00:00:00

abstract：:Histo-blood group epitopes are fucosylated branched oligosaccharides with well-defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group ant...

journal_title：ACS chemical biology

authors： Topin J,Lelimousin M,Arnaud J,Audfray A,Pérez S,Varrot A,Imberty A

更新日期：2016-07-15 00:00:00

abstract：:Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an essential role. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for removing the deaminated bases f...

journal_title：ACS chemical biology

authors： Zhang Z,Shen J,Yang Y,Li J,Cao W,Xie W

更新日期：2016-06-17 00:00:00

abstract：:New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to a...

journal_title：ACS chemical biology

authors： Drake CR,Sevillano N,Truillet C,Craik CS,VanBrocklin HF,Evans MJ

更新日期：2016-06-17 00:00:00

abstract：:The arabinosyltransferases responsible for the biosynthesis of the arabinan domains of two abundant heteropolysaccharides of the cell envelope of all mycobacterial species, lipoarabinomannan and arabinogalactan, are validated drug targets. Using a cell envelope preparation from Mycobacterium smegmatis as the enzyme so...

journal_title：ACS chemical biology

authors： Angala SK,McNeil MR,Zou L,Liav A,Zhang J,Lowary TL,Jackson M

更新日期：2016-06-17 00:00:00

abstract：:Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors have also been discovered, but their modes of binding and action remai...

journal_title：ACS chemical biology

authors： Shang Y,Yeatman HR,Provasi D,Alt A,Christopoulos A,Canals M,Filizola M

更新日期：2016-05-20 00:00:00

abstract：:Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal ...

journal_title：ACS chemical biology

authors： Bassenden AV,Rodionov D,Shi K,Berghuis AM

更新日期：2016-05-20 00:00:00

abstract：:Albicidin is a potent antibiotic and phytotoxin produced by Xanthomonas albilineans which targets the plant and bacterial DNA gyrase. We now report on a new albicidin derivative which is carbamoylated at the N-terminal coumaric acid by the action of the ATP-dependent O-carbamoyltransferase Alb15, present in the albici...

journal_title：ACS chemical biology

authors： Petras D,Kerwat D,Pesic A,Hempel BF,von Eckardstein L,Semsary S,Arasté J,Marguerettaz M,Royer M,Cociancich S,Süssmuth RD

更新日期：2016-05-20 00:00:00

abstract：:The abundant observation of chemical fragment information for molecular complexities is a major advantage of biological NMR analysis. Thus, the development of a novel technique for NMR signal assignment and metabolite identification may offer new possibilities for exploring molecular complexities. We propose a new sig...

journal_title：ACS chemical biology

authors： Ito K,Tsutsumi Y,Date Y,Kikuchi J

更新日期：2016-04-15 00:00:00

abstract：:The innate immune system provides the first line of defense against pathogens through the recognition of nonspecific patterns in RNA to protect the cell in a generalized way. The human RNA-activated protein kinase, PKR, is a dsRNA binding protein and an essential sensor in the innate immune response, which recognizes ...

journal_title：ACS chemical biology

authors： Hull CM,Anmangandla A,Bevilacqua PC

更新日期：2016-04-15 00:00:00

abstract：:Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β-cells...

journal_title：ACS chemical biology

authors： Kalwat MA,Huang Z,Wichaidit C,McGlynn K,Earnest S,Savoia C,Dioum EM,Schneider JW,Hutchison MR,Cobb MH

更新日期：2016-04-15 00:00:00

abstract：:Fusicoccin A is a diterpene glucoside phytotoxin generated by the fungal pathogen Phomopsis amygdali that causes the plant disease constriction canker, first discovered in New Jersey peach orchards in the 1930s. Fusicoccin A is also an emerging new lead in cancer chemotherapy. The hydrocarbon precursor of fusicoccin A...

journal_title：ACS chemical biology

authors： Chen M,Chou WK,Toyomasu T,Cane DE,Christianson DW

更新日期：2016-04-15 00:00:00

abstract：:RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In t...

journal_title：ACS chemical biology

authors： Schapira M

更新日期：2016-03-18 00:00:00

abstract：:Protein-fragment complementation assays (PCAs) are widely used for investigating protein interactions. However, the fragments used are structurally compromised and have not been optimized nor thoroughly characterized for accurately assessing these interactions. We took advantage of the small size and bright luminescen...

journal_title：ACS chemical biology

authors： Dixon AS,Schwinn MK,Hall MP,Zimmerman K,Otto P,Lubben TH,Butler BL,Binkowski BF,Machleidt T,Kirkland TA,Wood MG,Eggers CT,Encell LP,Wood KV

更新日期：2016-02-19 00:00:00

abstract：:Although peptide-based reporters of protein tyrosine kinase (PTK) activity have been used to study PTK enzymology in vitro, the application of these reporters to intracellular conditions is compromised by their dephosphorylation, preventing PTK activity measurements. Nonproteinogenic amino acids may be utilized to rat...

journal_title：ACS chemical biology

authors： Turner AH,Lebhar MS,Proctor A,Wang Q,Lawrence DS,Allbritton NL

更新日期：2016-02-19 00:00:00

abstract：:The anticancer molecule taxol (Paclitaxel) stands as one of the most medically and economically important natural products. However, despite decades of extensive study, its biosynthesis remains poorly understood. Unpredictable behavior of the first oxygenation enzyme, taxadiene-5α-hydroxylase, which produces a range o...

journal_title：ACS chemical biology

authors： Edgar S,Zhou K,Qiao K,King JR,Simpson JH,Stephanopoulos G

更新日期：2016-02-19 00:00:00

abstract：:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive pro...

journal_title：ACS chemical biology

authors： Childs-Disney JL,Disney MD

更新日期：2016-02-19 00:00:00

abstract：:Lanthipeptides are ribosomally synthesized and post-translationally modified peptides bearing the characteristic amino acids lanthionine and/or labionin. Here, we report on the discovery and characterization of the stackepeptins, produced by the Actinomycete Stackebrandtia nassauensis DSM-44728(T). The stackepeptins a...

journal_title：ACS chemical biology

authors： Jungmann NA,van Herwerden EF,Hügelland M,Süssmuth RD

更新日期：2016-01-15 00:00:00

abstract：:Intracellular reactions on nonenzymatic proteins that activate cellular signals are rarely found. We report one example here that a designed peptide derivative undergoes a nucleophilic reaction specifically with a cytosolic PDZ protein inside cells. This reaction led to the activation of ephrin-B reverse signaling, wh...

journal_title：ACS chemical biology

authors： Yu Y,Liu M,Ng TT,Huang F,Nie Y,Wang R,Yao ZP,Li Z,Xia J

更新日期：2016-01-15 00:00:00

abstract：:Simocyclinone D8 (1, SD8) has attracted attention due to its highly complex hybrid structure and the unusual way it inhibits bacterial DNA gyrase by preventing DNA binding to the enzyme. Although a hypothesis explaining simocyclinone biosynthesis has been previously proposed, little was proven in vivo due to the genet...

journal_title：ACS chemical biology

authors： Bilyk O,Brötz E,Tokovenko B,Bechthold A,Paululat T,Luzhetskyy A

更新日期：2016-01-15 00:00:00