Engineered EGF-A Peptides with Improved Affinity for Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9).

abstract：:Polyhalogenated dibenzo-p-dioxins are arguably among the most toxic molecules known to man. In addition to anthropogenic sources, marine invertebrates also harbor polybrominated dibenzo-p-dioxins of as yet unknown biogenic origin. Here, we report that the bmp gene locus in marine bacteria, a recently characterized sou...

journal_title：ACS chemical biology

authors： Agarwal V,Moore BS

更新日期：2014-09-19 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：: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：: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

authors： Olp MD,Sprague DJ,Goetz CJ,Kathman SG,Wynia-Smith SL,Shishodia S,Summers SB,Xu Z,Statsyuk AV,Smith BC

更新日期：2020-04-17 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：: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：: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：:We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE p...

journal_title：ACS chemical biology

authors： Karabadzhak AG,An M,Yao L,Langenbacher R,Moshnikova A,Adochite RC,Andreev OA,Reshetnyak YK,Engelman DM

更新日期：2014-11-21 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：: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：: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：:Methicillin resistance in Staphylococcus aureus depends on the production of mecA, which encodes penicillin-binding protein 2A (PBP2A), an acquired peptidoglycan transpeptidase (TP) with reduced susceptibility to β-lactam antibiotics. PBP2A cross-links nascent peptidoglycan when the native TPs are inhibited by β-lacta...

journal_title：ACS chemical biology

authors： Campbell J,Singh AK,Santa Maria JP Jr,Kim Y,Brown S,Swoboda JG,Mylonakis E,Wilkinson BJ,Walker S

更新日期：2011-01-21 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：:The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used t...

journal_title：ACS chemical biology

authors： Hoque MA,Zhang Y,Chen L,Yang G,Khatun MA,Chen H,Hao L,Feng Y

更新日期：2017-05-19 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

authors： Bechtel TJ,Li C,Kisty EA,Maurais AJ,Weerapana E

更新日期：2020-02-21 00:00:00

abstract：:The ATP site of kinases displays remarkable conformational flexibility when accommodating chemically diverse small molecule inhibitors. The so-called activation segment, whose conformation controls catalytic activity and access to the substrate binding pocket, can undergo a large conformational change with the active ...

journal_title：ACS chemical biology

authors： Zhao Z,Wu H,Wang L,Liu Y,Knapp S,Liu Q,Gray NS

更新日期：2014-06-20 00:00:00

abstract：:Small molecules are widely used in chemical biology without complete knowledge of their target profile, at risk of deriving conclusions that ignore potential confounding effects from unknown off-target interactions. The prediction and further experimental confirmation of novel affinities for PJ34 on Pim1 (IC(50) = 3.7...

journal_title：ACS chemical biology

authors： Antolín AA,Jalencas X,Yélamos J,Mestres J

更新日期：2012-12-21 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：:Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...

journal_title：ACS chemical biology

authors： Zahler NH

更新日期：2010-06-18 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：: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：:The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride s...

journal_title：ACS chemical biology

authors： Tomita T,Kim SY,Teramoto K,Meguro A,Ozaki T,Yoshida A,Motoyoshi Y,Mori N,Ishigami K,Watanabe H,Nishiyama M,Kuzuyama T

更新日期：2017-06-16 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 quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodyna...

journal_title：ACS chemical biology

authors： Tong M,Seeliger MA

更新日期：2015-01-16 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：: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：:Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptide...

journal_title：ACS chemical biology

authors： Li Y,Ducasse R,Zirah S,Blond A,Goulard C,Lescop E,Giraud C,Hartke A,Guittet E,Pernodet JL,Rebuffat S

更新日期：2015-11-20 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：:Developing computational tools for a chassis-centered biosynthetic pathway design is very important for a productive heterologous biosynthesis system by considering enormous foreign biosynthetic reactions. For many cases, a pathway to produce a target molecule consists of both native and heterologous reactions when ut...

journal_title：ACS chemical biology

authors： Ding S,Liao X,Tu W,Wu L,Tian Y,Sun Q,Chen J,Hu QN

更新日期：2017-11-17 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