abstract：:Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen...

journal_title：ACS chemical biology

authors： NaveenKumar SK,SharathBabu BN,Hemshekhar M,Kemparaju K,Girish KS,Mugesh G

更新日期：2018-08-17 00:00:00

abstract：:It is well established that aberrant cellular biochemical activity is strongly linked to the formation and progression of various cancers. Assays that could aid in cancer diagnostics, assessing anticancer drug resistance, and in the discovery of new anticancer drugs are highly warranted. In recent years, a large numbe...

journal_title：ACS chemical biology

authors： Singh K,Rotaru AM,Beharry AA

更新日期：2018-07-20 00:00:00

abstract：:Inducible modulation is often required for precise investigations and manipulations of dynamic biological processes. Transcription activator-like effectors (TALEs) provide a powerful tool for targeted gene editing and transcriptional programming. We designed a series of chemical inducible systems by coupling TALEs wit...

journal_title：ACS chemical biology

authors： Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Y

更新日期：2018-03-16 00:00:00

abstract：:Recent advances in understanding the relevance of noncoding RNA (ncRNA) to disease have increased interest in drugging ncRNA with small molecules. The recent discovery of ribocil, a structurally distinct synthetic mimic of the natural ligand of the flavin mononucleotide (FMN) riboswitch, has revealed the potential che...

journal_title：ACS chemical biology

authors： Rizvi NF,Howe JA,Nahvi A,Klein DJ,Fischmann TO,Kim HY,McCoy MA,Walker SS,Hruza A,Richards MP,Chamberlin C,Saradjian P,Butko MT,Mercado G,Burchard J,Strickland C,Dandliker PJ,Smith GF,Nickbarg EB

更新日期：2018-03-16 00:00:00

abstract：:Chloropupukeananin and chloropestolides are novel metabolites of the plant endophyte Pestalotiopsis fici, showing antimicrobial, antitumor, and anti-HIV activities. Their highly complex and unique skeletons were generated from the coisolated pestheic acid (1) and iso-A82775C (10) based on our previous studies. Here, w...

journal_title：ACS chemical biology

authors： Pan Y,Liu L,Guan F,Li E,Jin J,Li J,Che Y,Liu G

更新日期：2018-03-16 00:00:00

abstract：:Prenylated indole alkaloid okaramines selectively target insect glutamate-gated chloride channels (GluCls). Because of their highly complex structures, including azocine and azetidine rings, total synthesis of okaramine A or B has not been achieved, preventing evaluation of the biological activities of okaramines. Bio...

journal_title：ACS chemical biology

authors： Kato N,Furutani S,Otaka J,Noguchi A,Kinugasa K,Kai K,Hayashi H,Ihara M,Takahashi S,Matsuda K,Osada H

更新日期：2018-03-16 00:00:00

abstract：:Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by β-lactam antibiotics. We report herein our structural insights into catalysis by the essentia...

journal_title：ACS chemical biology

authors： Bernardo-García N,Mahasenan KV,Batuecas MT,Lee M,Hesek D,Petráčková D,Doubravová L,Branny P,Mobashery S,Hermoso JA

更新日期：2018-03-16 00:00:00

abstract：:Gene therapy is expected to be utilized for the treatment of various diseases. However, the spatiotemporal resolution of current gene therapy technology is not high enough. In this study, we generated a new technology for spatiotemporally controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques ...

journal_title：ACS chemical biology

authors： Takayama K,Mizuguchi H

更新日期：2018-02-16 00:00:00

abstract：:Originally discovered as part of an adaptive bacterial defense system against the invasion of foreign phages, programmable CRISPR-Cas nucleases have emerged as remarkable enzymes with transformative potential for both biological research and clinical application. CRISPR-Cas nucleases likely evolved in their natural co...

journal_title：ACS chemical biology

authors： Tsai SQ

更新日期：2018-02-16 00:00:00

abstract：:Next-generation DNA sequencing technologies have led to a massive accumulation of genomic and transcriptomic data from patients and healthy individuals. The major challenge ahead is to understand the functional significance of the elements of the human genome and transcriptome, and implications for diagnosis and treat...

journal_title：ACS chemical biology

authors： Kampmann M

更新日期：2018-02-16 00:00:00

abstract：:CRISPR-Cas genome editing technologies have revolutionized modern molecular biology by making targeted DNA edits simple and scalable. These technologies are developed by domesticating naturally occurring microbial adaptive immune systems that display wide diversity of functionality for targeted nucleic acid cleavage. ...

journal_title：ACS chemical biology

authors： Pyzocha NK,Chen S

更新日期：2018-02-16 00:00:00

abstract：:We recently reported two novel tools for precisely controlling and quantifying Cas9 activity: a chemically inducible Cas9 variant (ciCas9) that can be rapidly activated by small molecules and a ddPCR assay for time-resolved measurement of DNA double strand breaks (DSB-ddPCR). Here, we further demonstrate the potential...

journal_title：ACS chemical biology

authors： Rose JC,Stephany JJ,Wei CT,Fowler DM,Maly DJ

更新日期：2018-02-16 00:00:00

abstract：:Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor ...

journal_title：ACS chemical biology

authors： Mitchell AC,Alford SC,Hunter SA,Kannan D,Parra Sperberg RA,Chang CH,Cochran JR

更新日期：2018-01-19 00:00:00

abstract：:Desferrioxamine B (DFOB) was discovered in the late 1950s as a hydroxamic acid metabolite of the soil bacterium Streptomyces pilosus. The exquisite affinity of DFOB for Fe(III) identified its potential for removing excess iron from patients with transfusion-dependent hemoglobin disorders. Many studies have used semisy...

journal_title：ACS chemical biology

authors： Codd R,Richardson-Sanchez T,Telfer TJ,Gotsbacher MP

更新日期：2018-01-19 00:00:00

abstract：:Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of ...

journal_title：ACS chemical biology

authors： Khan E,Tawani A,Mishra SK,Verma AK,Upadhyay A,Kumar M,Sandhir R,Mishra A,Kumar A

更新日期：2018-01-19 00:00:00

abstract：:A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis...

journal_title：ACS chemical biology

authors： Zhu Z,Shaginian A,Grady LC,O'Keeffe T,Shi XE,Davie CP,Simpson GL,Messer JA,Evindar G,Bream RN,Thansandote PP,Prentice NR,Mason AM,Pal S

更新日期：2018-01-19 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：:RNAs are involved in interaction networks with other biomolecules and are crucial for proper cell function. Yet their biochemical analysis remains challenging. For Förster Resonance Energy Transfer (FRET), a common tool to study such interaction networks, two interacting molecules have to be fluorescently labeled. "Sp...

journal_title：ACS chemical biology

authors： Roszyk L,Kollenda S,Hennig S

更新日期：2017-12-15 00:00:00

abstract：:The rational design of environmentally sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The de...

journal_title：ACS chemical biology

authors： Shaya J,Collot M,Bénailly F,Mahmoud N,Mély Y,Michel BY,Klymchenko AS,Burger A

更新日期：2017-12-15 00:00:00

abstract：:Ebselen modulates target proteins through redox reactions with selenocysteine/cysteine residues, or through binding to the zinc finger domains. However, a recent contradiction in ebselen inhibition of kidney type glutaminase (KGA) stimulated our interest in investigating its inhibition mechanism with glutamate dehydro...

journal_title：ACS chemical biology

authors： Yu Y,Jin Y,Zhou J,Ruan H,Zhao H,Lu S,Zhang Y,Li D,Ji X,Ruan BH

更新日期：2017-12-15 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：: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：:Flavin-containing monooxygenases (FMOs) are emerging as effective players in oxidative drug metabolism. Until recently, the functions of the five human FMO isoforms were mostly linked to their capability of oxygenating molecules containing soft N- and S-nucleophiles. However, the human FMO isoform 5 was recently shown...

journal_title：ACS chemical biology

authors： Fiorentini F,Romero E,Fraaije MW,Faber K,Hall M,Mattevi A

更新日期：2017-09-15 00:00:00

abstract：:Gaussia luciferase (GLUC) is a bioluminescent reporter protein of increasing importance. As a secretory protein, it has increased sensitivity in vitro and in vivo (∼20 000-fold, and ∼1000-fold, respectively) over its competitor, secreted alkaline phosphatase. Unfortunately, this same advantageous secretory nature of G...

journal_title：ACS chemical biology

authors： Gaur S,Bhargava-Shah A,Hori S,Afjei R,Sekar TV,Gambhir SS,Massoud TF,Paulmurugan R

更新日期：2017-09-15 00:00:00

abstract：:Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for a mechanism of act...

journal_title：ACS chemical biology

authors： Santa Maria JP Jr,Park Y,Yang L,Murgolo N,Altman MD,Zuck P,Adam G,Chamberlin C,Saradjian P,Dandliker P,Boshoff HIM,Barry CE 3rd,Garlisi C,Olsen DB,Young K,Glick M,Nickbarg E,Kutchukian PS

更新日期：2017-09-15 00:00:00

abstract：:Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to all...

journal_title：ACS chemical biology

authors： Cornilescu G,Ramos Alvarenga RF,Wyche TP,Bugni TS,Gil RR,Cornilescu CC,Westler WM,Markley JL,Schwieters CD

更新日期：2017-08-18 00:00:00

abstract：:We have developed a chemically controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in ...

journal_title：ACS chemical biology

authors： Schneider EL,Hearn BR,Pfaff SJ,Reid R,Parkes DG,Vrang N,Ashley GW,Santi DV

更新日期：2017-08-18 00:00:00

abstract：:Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...

journal_title：ACS chemical biology

authors： Vannecke W,Ampe C,Van Troys M,Beltramo M,Madder A

更新日期：2017-08-18 00:00:00

abstract：:The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their effi...

journal_title：ACS chemical biology

authors： Poh WH,Barraud N,Guglielmo S,Lazzarato L,Rolando B,Fruttero R,Rice SA

更新日期：2017-08-18 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：:Many pathogenic bacteria including Staphylococcus aureus use iron-chelating siderophores to acquire iron. Iron uptake oxidoreductase (IruO), a flavin adenine dinucleotide (FAD)-containing nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase from S. aureus, functions as a reductase for IsdG and IsdI,...

journal_title：ACS chemical biology

authors： Kobylarz MJ,Heieis GA,Loutet SA,Murphy MEP

更新日期：2017-07-21 00:00:00

abstract：:A class of new glycan-reactive broadly neutralizing antibodies represented by PGT121, 10-1074, and PGT128 has recently been discovered that targets specific N-glycans and the peptide region around the V3 domain. However, the glycan specificity and fine epitopes of these bNAbs remain to be further defined. We report he...

journal_title：ACS chemical biology

authors： Orwenyo J,Cai H,Giddens J,Amin MN,Toonstra C,Wang LX

更新日期：2017-06-16 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：:Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, ...

journal_title：ACS chemical biology

authors： Xiong J,Liu X,Cheng QY,Xiao S,Xia LX,Yuan BF,Feng YQ

更新日期：2017-06-16 00:00:00

abstract：:Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of g...

journal_title：ACS chemical biology

authors： Nasir W,Frank M,Kunze A,Bally M,Parra F,Nyholm PG,Höök F,Larson G

更新日期：2017-05-19 00:00:00

abstract：:Proprotein convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of several pathologies including cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present the fi...

journal_title：ACS chemical biology

authors： Dahms SO,Jiao GS,Than ME

更新日期：2017-05-19 00:00:00

abstract：:A two-way colorimetric biosensor based on unmodified gold nanoparticles (GNPs) and a switchable double-stranded DNA (dsDNA) concatemer have been demonstrated. Two hairpin probes (H1 and H2) were first designed that provided the fuels to assemble the dsDNA concatemers via hybridization chain reaction (HCR). A functiona...

journal_title：ACS chemical biology

authors： Zhu L,Shao X,Luo Y,Huang K,Xu W

更新日期：2017-05-19 00:00:00

abstract：:The β-hydroxylation of l-histidine is the first step in the biosynthesis of the imidazolone base of the antifungal drug nikkomycin. The cytochrome P450 (NikQ) hydroxylates the amino acid while it is appended via a phosphopantetheine linker to the non-ribosomal peptide synthetase (NRPS) NikP1. The latter enzyme is comp...

journal_title：ACS chemical biology

authors： Wise CE,Makris TM

更新日期：2017-05-19 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：:Insights into the thermodynamic and kinetic signature of the transient opening of a protein-binding pocket resulting from accommodation of suitable substituents attached to a given parent ligand scaffold are presented. As a target, we selected human aldose reductase, an enzyme involved in the development of late-stage...

journal_title：ACS chemical biology

authors： Rechlin C,Scheer F,Terwesten F,Wulsdorf T,Pol E,Fridh V,Toth P,Diederich WE,Heine A,Klebe G

更新日期：2017-05-19 00:00:00