Revealing coupling patterns in isoprenoid alkylation biocatalysis.

abstract：:A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small...

journal_title：ACS chemical biology

authors： Gaffney A,Nangarlia A,Ang CG,Gossert S,Rashad Ahmed AA,Hossain MA,Abrams CF,Smith AB 3rd,Chaiken I

更新日期：2021-01-15 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：:The 3D structure of a protein is determined by the unique sequence of amino acid residues comprising the polypeptide chain. Sequence changes can cause protein misfolding, a potentially toxic phenomenon implicated in various neurodegenerative disorders. In a recent paper, translational misincorporation is proposed to b...

journal_title：ACS chemical biology

authors： Rochet JC

更新日期：2006-10-24 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：:To combat the increasing spread of antimicrobial resistance and the shortage of novel anti-infectives, one strategy for the development of new antibiotics is to optimize known chemical scaffolds. Here, we focus on the biosynthetic engineering of Amycolatopsis sulphurea for derivatization of the atypical tetracycline c...

journal_title：ACS chemical biology

authors： Lukežič T,Fayad AA,Bader C,Harmrolfs K,Bartuli J,Groß S,Lešnik U,Hennessen F,Herrmann J,Pikl Š,Petković H,Müller R

更新日期：2019-03-15 00:00:00

abstract：:The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimeth...

journal_title：ACS chemical biology

authors： Walsh CT

更新日期：2014-12-19 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：:The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights fro...

journal_title：ACS chemical biology

authors： Daeffler KN,Lester HA,Dougherty DA

更新日期：2014-10-17 00:00:00

abstract：:Whereas the C. elegans genome was sequenced many years ago, the role of small molecule signals in its biology is still poorly understood. A recent publication reports the identification of two steroidal signaling molecules that regulate C. elegans reproductive development and dauer diapause via the nuclear receptor DA...

journal_title：ACS chemical biology

authors： Schroeder FC

更新日期：2006-05-23 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：:In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing islet β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 is a supramolecular tool for selective complexation of K residues in (poly)peptides. ...

journal_title：ACS chemical biology

authors： Lopes DH,Attar A,Nair G,Hayden EY,Du Z,McDaniel K,Dutt S,Bravo-Rodriguez K,Mittal S,Klärner FG,Wang C,Sanchez-Garcia E,Schrader T,Bitan G

更新日期：2015-06-19 00:00:00

abstract：:Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The current treatment options for AD are limited to ameliorating cognitive decline temporarily and not reversing or preventing the progression of dementia. Hence, more effective therapeutic strategies are needed ...

journal_title：ACS chemical biology

authors： Krishnan N,Chen X,Donnelly-Roberts D,Mohler EG,Holtzman DM,Gopalakrishnan SM

更新日期：2020-12-18 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：: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

abstract：:Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cel...

journal_title：ACS chemical biology

authors： Libby CJ,Zhang S,Benavides GA,Scott SE,Li Y,Redmann M,Tran AN,Otamias A,Darley-Usmar V,Napierala M,Zhang J,Augelli-Szafran CE,Zhang W,Hjelmeland AB

更新日期：2018-08-17 00:00:00

abstract：:The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the B...

journal_title：ACS chemical biology

authors： Miller TC,Rutherford TJ,Birchall K,Chugh J,Fiedler M,Bienz M

更新日期：2014-12-19 00:00:00

abstract：:Allosteric inhibitors can be more difficult to optimize without an understanding of how their binding influences the conformational motions of the target. Here, we used an integrated computational and experimental approach to probe the molecular mechanism of an allosteric inhibitor of heat shock protein 70 (Hsp70). Th...

journal_title：ACS chemical biology

authors： Rinaldi S,Assimon VA,Young ZT,Morra G,Shao H,Taylor IR,Gestwicki JE,Colombo G

更新日期：2018-11-16 00:00:00

abstract：:Human alkyladenine DNA glycosylase (AAG) initiates the base excision repair pathway by excising alkylated and deaminated purine lesions. In vitro biochemical experiments demonstrate that AAG uses facilitated diffusion to efficiently search DNA to find rare sites of damage and suggest that electrostatic interactions ar...

journal_title：ACS chemical biology

authors： Zhang Y,O'Brien PJ

更新日期：2015-11-20 00:00:00

abstract：:New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of R...

journal_title：ACS chemical biology

authors： Kudo K,Koiwai H,Kagaya N,Nishiyama M,Kuzuyama T,Shin-Ya K,Ikeda H

更新日期：2019-06-21 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：:Reactive oxygen species (ROS) play an important role in the onset of Parkinson's disease (PD), and deciphering protective mechanisms is a major goal for therapeutic development. Here, DJ-1 (PARK7) gained major attention when a conserved cysteine residue with a putative role in oxidative stress sensing/protection was l...

journal_title：ACS chemical biology

authors： Drechsel J,Mandl FA,Sieber SA

更新日期：2018-08-17 00:00:00

abstract：:Signal transducer and activator of transcription (STAT) proteins have important biological functions; however, deregulation of STAT signaling is a driving force behind the onset and progression of inflammatory diseases and cancer. While their biological roles suggest that STAT proteins would be valuable targets for de...

journal_title：ACS chemical biology

authors： Attarha S,Reithmeier A,Busker S,Desroses M,Page BDG

更新日期：2020-07-17 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：: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：:Miniproteins have a size between that of larger biologics and small molecules and presumably possess the advantages of both; they represent an expanding class of promising scaffolds for the design of affinity reagents, enzymes, and therapeutics. Conventional strategies to promote cellular uptake of miniproteins rely o...

journal_title：ACS chemical biology

authors： Meng X,Li T,Zhao Y,Wu C

更新日期：2018-11-16 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：:HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-inte...

journal_title：ACS chemical biology

authors： Sattin S,Daghetti A,Thépaut M,Berzi A,Sánchez-Navarro M,Tabarani G,Rojo J,Fieschi F,Clerici M,Bernardi A

更新日期：2010-03-19 00:00:00

abstract：:Dihydrofolate reductase (DHFR) is a potential drug target for Trypanosoma brucei, a human parasite, which is the causative agent for African sleeping sickness. No drug is available against this target, since none of the classical antifolates such as pyrimethamine (PYR), cycloguanil, or trimethoprim are effective as se...

journal_title：ACS chemical biology

authors： Vanichtanankul J,Taweechai S,Yuvaniyama J,Vilaivan T,Chitnumsub P,Kamchonwongpaisan S,Yuthavong Y

更新日期：2011-09-16 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：: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