abstract：:The molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically,...

journal_title：ACS chemical biology

authors： Hall JA,Kusuma BR,Brandt GE,Blagg BS

更新日期：2014-04-18 00:00:00

abstract：:N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. In...

journal_title：ACS chemical biology

authors： Daniels AD,Campeotto I,van der Kamp MW,Bolt AH,Trinh CH,Phillips SE,Pearson AR,Nelson A,Mulholland AJ,Berry A

更新日期：2014-04-18 00:00:00

abstract：:We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infe...

journal_title：ACS chemical biology

authors： Zhang HM,Dai H,Hanson PJ,Li H,Guo H,Ye X,Hemida MG,Wang L,Tong Y,Qiu Y,Liu S,Wang F,Song F,Zhang B,Wang JG,Zhang LX,Yang D

更新日期：2014-04-18 00:00:00

abstract：:Dopamine, a biogenic amine with important biological functions, is produced from l-DOPA by DOPA decarboxylase (DDC). DDC is a potential target to modulate the production of dopamine in several pathological states. Known inhibitors of DDC have been used for treatment of Parkinson's disease but suffered low specificity ...

journal_title：ACS chemical biology

authors： Ren J,Zhang Y,Jin H,Yu J,Zhou Y,Wu F,Zhang W

更新日期：2014-04-18 00:00:00

abstract：:Activation by glycosaminoglycans (GAGs) is an emerging trend among extracellular proteases important in disease. ProMMP-7, the zymogen of a matrix metalloproteinase secreted by mucosal epithelial and tumor cells, is activated at their surfaces by sulfated GAGs, but how? ProMMP-7 is activated in trans by representative...

journal_title：ACS chemical biology

authors： Fulcher YG,Sanganna Gari RR,Frey NC,Zhang F,Linhardt RJ,King GM,Van Doren SR

更新日期：2014-04-18 00:00:00

abstract：:Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease of impoverished populations in countries where funds are limited for research and patient care. However, the health burden of individuals in endemic areas man...

journal_title：ACS chemical biology

authors： Sharlow ER,Leimgruber S,Murray S,Lira A,Sciotti RJ,Hickman M,Hudson T,Leed S,Caridha D,Barrios AM,Close D,Grögl M,Lazo JS

更新日期：2014-03-21 00:00:00

abstract：:Sublancin 168 is a member of a small group of glycosylated antimicrobial peptides known as glycocins. The solution structure of sublancin 168, a 37-amino-acid peptide produced by Bacillus subtilis 168, has been solved by nuclear magnetic resonance (NMR) spectroscopy. Sublancin comprises two α-helices and a well-define...

journal_title：ACS chemical biology

authors： Garcia De Gonzalo CV,Zhu L,Oman TJ,van der Donk WA

更新日期：2014-03-21 00:00:00

abstract：:Photoinduced cross-linking (PIC) has become a powerful tool in chemical biology for the identification and mapping of stable or transient interactions between biomacromolecules and their (unknown) ligands. However, the value of PIC for in vitro and in vivo structural proteomics can be realized only if cross-linking re...

journal_title：ACS chemical biology

authors： Preston GW,Radford SE,Ashcroft AE,Wilson AJ

更新日期：2014-03-21 00:00:00

abstract：:A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...

journal_title：ACS chemical biology

authors： Yang YL,Lee YP,Yang YL,Lin PC

更新日期：2014-02-21 00:00:00

abstract：:Many cellular processes are regulated by posttranslational modifications that are recognized by specific domains in protein binding partners. These interactions are often weak, thus allowing a highly dynamic and combinatorial regulatory network of protein-protein interactions. We report an efficient strategy that over...

journal_title：ACS chemical biology

authors： Tripsianes K,Chu NK,Friberg A,Sattler M,Becker CF

更新日期：2014-02-21 00:00:00

abstract：:Protein arginine N-methyltransferase 3 (PRMT3) belongs to the family of type I PRMTs and harbors the activity to use S-adenosyl-l-methionine (SAM) as a methyl-donor cofactor for protein arginine labeling. However, PRMT3's functions remain elusive with the lacked knowledge of its target scope in cellular settings. Insp...

journal_title：ACS chemical biology

authors： Guo H,Wang R,Zheng W,Chen Y,Blum G,Deng H,Luo M

更新日期：2014-02-21 00:00:00

abstract：:Enzymatic transfer of the AMP portion of ATP to substrate proteins has recently been described as an essential mechanism of bacterial infection for several pathogens. The first AMPylator to be discovered, VopS from Vibrio parahemolyticus, catalyzes the transfer of AMP onto the host GTPases Cdc42 and Rac1. Modification...

journal_title：ACS chemical biology

authors： Lewallen DM,Sreelatha A,Dharmarajan V,Madoux F,Chase P,Griffin PR,Orth K,Hodder P,Thompson PR

更新日期：2014-02-21 00:00:00

abstract：:The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising and clinically unexploited antibiotic targets for treatment of multidrug-resistant Gram-negative infections. Progress in medicinal chemistry has led to the discovery of potent LpxC inhibitors with a variety of chemical scaffolds and disti...

journal_title：ACS chemical biology

authors： Lee CJ,Liang X,Gopalaswamy R,Najeeb J,Ark ED,Toone EJ,Zhou P

更新日期：2014-01-17 00:00:00

abstract：:A complication of diabetes is the inability of wounds to heal in diabetic patients. Diabetic wounds are refractory to healing due to the involvement of activated matrix metalloproteinases (MMPs), which remodel the tissue resulting in apoptosis. There are no readily available methods that identify active unregulated MM...

journal_title：ACS chemical biology

authors： Gooyit M,Peng Z,Wolter WR,Pi H,Ding D,Hesek D,Lee M,Boggess B,Champion MM,Suckow MA,Mobashery S,Chang M

更新日期：2014-01-17 00:00:00

abstract：:Protein dimerization provides a mechanism for the modulation of cellular signaling events. In α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, the rapidly desensitizing, activated state has been correlated with a weakly dimeric, glutamate-binding domain conformation. Allosteric modulators can fo...

journal_title：ACS chemical biology

authors： Ptak CP,Hsieh CL,Weiland GA,Oswald RE

更新日期：2014-01-17 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：: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：:Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex pr...

journal_title：ACS chemical biology

authors： Unudurthi SD,Hotta K,Kim CY

更新日期：2013-11-15 00:00:00

abstract：:Seasonal and pandemic influenza viruses continue to be a leading global health concern. Emerging resistance to the current drugs and the variable efficacy of vaccines underscore the need for developing new flu drugs that will be broadly effective against wild-type and drug-resistant influenza strains. Here, we report ...

journal_title：ACS chemical biology

authors： Bauman JD,Patel D,Baker SF,Vijayan RS,Xiang A,Parhi AK,Martínez-Sobrido L,LaVoie EJ,Das K,Arnold E

更新日期：2013-11-15 00:00:00

abstract：:Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of...

journal_title：ACS chemical biology

authors： Rzuczek SG,Gao Y,Tang ZZ,Thornton CA,Kodadek T,Disney MD

更新日期：2013-10-18 00:00:00

abstract：:A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a cha...

journal_title：ACS chemical biology

authors： Parkinson EI,Bair JS,Cismesia M,Hergenrother PJ

更新日期：2013-10-18 00:00:00

abstract：:X-ray crystallographic analysis of a bovine antibody (BLV1H12) revealed a unique scaffold in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent exposed, antiparallel β-stranded "stalk" fused with a disulfide cross-linked "knob" domain. This unusual variable region motif pr...

journal_title：ACS chemical biology

authors： Zhang Y,Wang D,Welzel G,Wang Y,Schultz PG,Wang F

更新日期：2013-10-18 00:00:00

abstract：:One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote th...

journal_title：ACS chemical biology

authors： Molzan M,Kasper S,Röglin L,Skwarczynska M,Sassa T,Inoue T,Breitenbuecher F,Ohkanda J,Kato N,Schuler M,Ottmann C

更新日期：2013-09-20 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：:Dicamba monooxygenase (DMO) catalyzes the O-demethylation of dicamba (3,6-dichloro-2-methoxybenzoate) to produce 3,6-dichlorosalicylate and formaldehyde. Recent crystallographic studies suggest that DMO catalyzes the challenging oxidation of a saturated C-H bond within the methyl group of dicamba to form a hemiacetal ...

journal_title：ACS chemical biology

authors： Jiang W,Wilson MA,Weeks DP

更新日期：2013-08-16 00:00:00

abstract：:The cell utilizes the Keap1/Nrf2-ARE signaling pathway to detoxify harmful chemicals in order to protect itself from oxidative stress and to maintain its reducing environment. When exposed to oxidative stress and xenobiotic inducers, the redox sensitive Keap1 is covalently modified at specific cysteine residues. Conse...

journal_title：ACS chemical biology

authors： Wang R,Mason DE,Choe KP,Lewin AS,Peters EC,Luesch H

更新日期：2013-08-16 00:00:00

abstract：:Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing bimodular and trimodular nonribosomal peptide synthetase (NRPS) assembly ...

journal_title：ACS chemical biology

authors： Walsh CT,Haynes SW,Ames BD,Gao X,Tang Y

更新日期：2013-07-19 00:00:00

abstract：:RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...

journal_title：ACS chemical biology

authors： Xu D,Young JH,Krahn JM,Song D,Corbett KD,Chazin WJ,Pedersen LC,Esko JD

更新日期：2013-07-19 00:00:00

abstract：:We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed f...

journal_title：ACS chemical biology

authors： Prakash TP,Lima WF,Murray HM,Elbashir S,Cantley W,Foster D,Jayaraman M,Chappell AE,Manoharan M,Swayze EE,Crooke ST

更新日期：2013-07-19 00:00:00

abstract：:The Siglec family of sialic acid-binding proteins are differentially expressed on white blood cells of the immune system and represent an attractive class of targets for cell-directed therapy. Nanoparticles decorated with high-affinity Siglec ligands show promise for delivering cargo to Siglec-bearing cells, but this ...

journal_title：ACS chemical biology

authors： Rillahan CD,Schwartz E,Rademacher C,McBride R,Rangarajan J,Fokin VV,Paulson JC

更新日期：2013-07-19 00:00:00

abstract：:The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, ...

journal_title：ACS chemical biology

authors： Chowdhury R,Candela-Lena JI,Chan MC,Greenald DJ,Yeoh KK,Tian YM,McDonough MA,Tumber A,Rose NR,Conejo-Garcia A,Demetriades M,Mathavan S,Kawamura A,Lee MK,van Eeden F,Pugh CW,Ratcliffe PJ,Schofield CJ

更新日期：2013-07-19 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：:Although protein kinase inhibitors present excellent pharmaceutical opportunities, lack of selectivity and associated therapeutic side effects are common. Bisubstrate-based inhibitors targeting both the high-selectivity peptide substrate binding groove and the high-affinity ATP pocket address this. However, they are t...

journal_title：ACS chemical biology

authors： van Wandelen LT,van Ameijde J,Ismail-Ali AF,van Ufford HC,Vijftigschild LA,Beekman JM,Martin NI,Ruijtenbeek R,Liskamp RM

更新日期：2013-07-19 00:00:00

abstract：:miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have d...

journal_title：ACS chemical biology

authors： Bose D,Jayaraj GG,Kumar S,Maiti S

更新日期：2013-05-17 00:00:00

abstract：:Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to ide...

journal_title：ACS chemical biology

authors： Adams DJ,Boskovic ZV,Theriault JR,Wang AJ,Stern AM,Wagner BK,Shamji AF,Schreiber SL

更新日期：2013-05-17 00:00:00

abstract：:Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investig...

journal_title：ACS chemical biology

authors： Ho PI,Yue K,Pandey P,Breault L,Harbinski F,McBride AJ,Webb B,Narahari J,Karassina N,Wood KV,Hill A,Auld DS

更新日期：2013-05-17 00:00:00

abstract：:The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociati...

journal_title：ACS chemical biology

authors： Bjelic S,Nivón LG,Çelebi-Ölçüm N,Kiss G,Rosewall CF,Lovick HM,Ingalls EL,Gallaher JL,Seetharaman J,Lew S,Montelione GT,Hunt JF,Michael FE,Houk KN,Baker D

更新日期：2013-04-19 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：:Bioorthogonal ligation methods that allow the selective conjugation of fluorophores or biotin to proteins and small molecule probes that contain inert chemical handles are an important component of many chemical proteomic strategies. Here, we present a new catch-and-release enrichment strategy that utilizes a hexylchl...

journal_title：ACS chemical biology

authors： Brigham JL,Perera BG,Maly DJ

更新日期：2013-04-19 00:00:00

abstract：:G protein-coupled receptors (GPCRs) are an ubiquitously expressed class of transmembrane proteins involved in the signal transduction of neurotransmitters, hormones and various other ligands. Their signaling output is desensitized by mechanisms involving phosphorylation, internalization, and dissociation from G protei...

journal_title：ACS chemical biology

authors： Gehret AU,Hinkle PM

更新日期：2013-03-15 00:00:00