Bacterial evolution by intelligent design.

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：: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：:The Akt kinase family, consisting of three isoforms in humans, is a well-validated class of drug target. Through various screening campaigns in academics and pharmaceutical industries, several promising inhibitors have been developed to date. However, due to the mechanistic and structural similarities of Akt kinases, ...

journal_title：ACS chemical biology

authors： Hayashi Y,Morimoto J,Suga H

更新日期：2012-03-16 00:00:00

abstract：:Regulators of G protein signaling (RGS) proteins are key players in regulating signaling via G protein-coupled receptors. RGS proteins directly bind to the Gα-subunits of activated heterotrimeric G-proteins, and accelerate the rate of GTP hydrolysis, thereby rapidly deactivating G-proteins. Using atomistic simulations...

journal_title：ACS chemical biology

authors： Vashisth H,Storaska AJ,Neubig RR,Brooks CL 3rd

更新日期：2013-12-20 00:00:00

abstract：:Chemical synthesis is a powerful method for precise modification of the structural and electronic properties of proteins. The difficulties in the synthesis and purification of peptides containing transmembrane segments have presented obstacles to the chemical synthesis of integral membrane proteins. Here, we present a...

journal_title：ACS chemical biology

authors： Komarov AG,Linn KM,Devereaux JJ,Valiyaveetil FI

更新日期：2009-12-18 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

authors： Wienen-Schmidt B,Schmidt D,Gerber HD,Heine A,Gohlke H,Klebe G

更新日期：2019-12-20 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

abstract：:The complexity of the human proteome is greatly expanded by post-translational modifications. New tools capable of recognizing these modifications in a sequence-specific fashion provide a route to purify these modified proteins, to alter protein trafficking, and to visualize signal transduction in real time. Here, we ...

journal_title：ACS chemical biology

authors： Olson CA,Liao HI,Sun R,Roberts RW

更新日期：2008-08-15 00:00:00

abstract：:The number of bacterial strains that are resistant against antibiotics increased dramatically during the past decades. This fact stresses the urgent need for the development of new antibacterial agents with novel modes of action targeting essential enzymes such as RNA polymerase (RNAP). Bacterial RNAP is a large multi...

journal_title：ACS chemical biology

authors： Hüsecken K,Negri M,Fruth M,Boettcher S,Hartmann RW,Haupenthal J

更新日期：2013-04-19 00:00:00

abstract：:Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ω-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lip...

journal_title：ACS chemical biology

authors： Beavers WN,Rose KL,Galligan JJ,Mitchener MM,Rouzer CA,Tallman KA,Lamberson CR,Wang X,Hill S,Ivanova PT,Brown HA,Zhang B,Porter NA,Marnett LJ

更新日期：2017-08-18 00:00:00

abstract：:Replacing the two Mn(2+) ions normally present in human Arginase I with Co(2+) resulted in a significantly lowered K(M) value without a concomitant reduction in k(cat). In addition, the pH dependence of the reaction was shifted from a pK(a) of 8.5 to a pK(a) of 7.5. The combination of these effects led to a 10-fold in...

journal_title：ACS chemical biology

authors： Stone EM,Glazer ES,Chantranupong L,Cherukuri P,Breece RM,Tierney DL,Curley SA,Iverson BL,Georgiou G

更新日期：2010-03-19 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：: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

authors： Stepanova R,Inagi H,Sugawara K,Asada K,Nishi T,Ueda D,Yasuno Y,Shinada T,Miki K,Fujihashi M,Sato T

更新日期：2020-06-19 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：:Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also ...

journal_title：ACS chemical biology

authors： Yuan Y,Wang Q,Paulk J,Kubicek S,Kemp MM,Adams DJ,Shamji AF,Wagner BK,Schreiber SL

更新日期：2012-07-20 00:00:00

abstract：:Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters, although the mechanism of internalization remains unclear. Here, we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin (biotinGNeo), a low molecular weight guanidinium-rich molecular transporter. ...

journal_title：ACS chemical biology

authors： Inoue M,Tong W,Esko JD,Tor Y

更新日期：2013-07-19 00:00:00

abstract：:Detection of metabolites and post-translational modifications can be achieved using the azide as a bioorthogonal chemical reporter. Once introduced into target biomolecules, either metabolically or through chemical modification, the azide can be tagged with probes using one of three highly selective reactions: the Sta...

journal_title：ACS chemical biology

authors： Agard NJ,Baskin JM,Prescher JA,Lo A,Bertozzi CR

更新日期：2006-11-21 00:00:00

abstract：:Invertebrate animal models (mainly the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) are gaining momentum as screening tools in drug discovery. These organisms combine genetic amenability, low cost, and culture conditions compatible with large-scale screens. Their main advantage is to allo...

journal_title：ACS chemical biology

authors： Ségalat L

更新日期：2007-04-24 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：:Targeting native progenitors with small molecule pharmaceuticals that direct cell fate decisions is an attractive approach for regenerative medicine. Here, we show that 3,5-disubstituted isoxazoles (Isx), stem cell-modulator small molecules originally recovered in a P19 embryonal carcinoma cell-based screen, directed ...

journal_title：ACS chemical biology

authors： Russell JL,Goetsch SC,Aguilar HR,Frantz DE,Schneider JW

更新日期：2012-06-15 00:00:00

abstract：:Functionally selective ligands stabilize conformations of G protein-coupled receptors (GPCRs) that induce a preference for signaling via a subset of the intracellular pathways activated by the endogenous agonists. The possibility to fine-tune the functional activity of a receptor provides opportunities to develop drug...

journal_title：ACS chemical biology

authors： Männel B,Jaiteh M,Zeifman A,Randakova A,Möller D,Hübner H,Gmeiner P,Carlsson J

更新日期：2017-10-20 00:00:00

abstract：:Antivirulence strategies addressing bacterial pathogenicity without exhibiting growth inhibition effects represent a novel approach to overcome today's crisis in antibiotic development. In recent studies, we examined various inhibitors of PqsD, an enzyme involved in formation of Pseudomonas aeruginosa cell-to-cell sig...

journal_title：ACS chemical biology

authors： Storz MP,Brengel C,Weidel E,Hoffmann M,Hollemeyer K,Steinbach A,Müller R,Empting M,Hartmann RW

更新日期：2013-12-20 00:00:00

abstract：:The ubiquity of microorganisms is unparalleled in any other known organism. These creatures surround our outsides and colonize our insides, a fact that has been known for centuries. However, despite their prevalence and long study, many of their characteristics still remain largely unexplained, including how proteins ...

journal_title：ACS chemical biology

authors： Brownlee C

更新日期：2010-07-16 00:00:00

abstract：:In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nu...

journal_title：ACS chemical biology

authors： Hintersteiner M,Ambrus G,Bednenko J,Schmied M,Knox AJ,Meisner NC,Gstach H,Seifert JM,Singer EL,Gerace L,Auer M

更新日期：2010-10-15 00:00:00

abstract：:The goal of incorporating renewable carbon into the fuel and chemical enterprise will most likely be successful when combined systems of biocatalysts and chemical catalysts are exploited. Significant efforts in the biocatalytic release of sugars from biomass are being pursued for subsequent use in fermentation. Two re...

journal_title：ACS chemical biology

authors： Shanks BH

更新日期：2007-08-17 00:00:00

abstract：:Methods for the rapid identification of defined cell growth conditions are lacking. This deficiency is a major barrier to the investigation and application of human embryonic stem (ES) cells. To address this problem, we developed a method for generating arrays of self-assembled monolayers (SAMs) in which each element ...

journal_title：ACS chemical biology

authors： Derda R,Li L,Orner BP,Lewis RL,Thomson JA,Kiessling LL

更新日期：2007-05-22 00:00:00

abstract：:Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics method...

journal_title：ACS chemical biology

authors： Olson DE,Udeshi ND,Wolfson NA,Pitcairn CA,Sullivan ED,Jaffe JD,Svinkina T,Natoli T,Lu X,Paulk J,McCarren P,Wagner FF,Barker D,Howe E,Lazzaro F,Gale JP,Zhang YL,Subramanian A,Fierke CA,Carr SA,Holson EB

更新日期：2014-10-17 00:00:00

abstract：:The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

journal_title：ACS chemical biology

authors： Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

更新日期：2017-12-15 00:00:00

abstract：:Protein phosphatases are critical regulators of cellular signaling in both eukaryotes and prokaryotes. The majority of protein phosphatases dephosphorylate phosphoserine/phosphothreonine or phosphotyrosine residues. Recently, however, YwlE, a member of the low-molecular weight protein tyrosine phosphatase (LMW-PTP) fa...

journal_title：ACS chemical biology

authors： Fuhrmann J,Subramanian V,Thompson PR

更新日期：2013-09-20 00:00:00

abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...

journal_title：ACS chemical biology

authors： de Paz JL,Moseman EA,Noti C,Polito L,von Andrian UH,Seeberger PH

更新日期：2007-11-20 00:00:00