abstract：:GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets. However, little is known about their activation mechanisms due to the difficulty in purification. Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membran...

journal_title：ACS chemical biology

authors： Mitra N,Liu Y,Liu J,Serebryany E,Mooney V,DeVree BT,Sunahara RK,Yan EC

更新日期：2013-03-15 00:00:00

abstract：:Cysteine residues on proteins play key roles in catalysis and regulation. These functional cysteines serve as active sites for nucleophilic and redox catalysis, sites of allosteric regulation, and metal-binding ligands on proteins from diverse classes including proteases, kinases, metabolic enzymes, and transcription ...

journal_title：ACS chemical biology

authors： Pace NJ,Weerapana E

更新日期：2013-02-15 00:00:00

abstract：:Caenorhabditis elegans lives in compost and decaying fruit, eats bacteria and is exposed to pathogenic microbes. We show that C. elegans is able to modify diverse microbial small-molecule toxins via both O- and N-glucosylation as well as unusual 3'-O-phosphorylation of the resulting glucosides. The resulting glucosyla...

journal_title：ACS chemical biology

authors： Stupp GS,von Reuss SH,Izrayelit Y,Ajredini R,Schroeder FC,Edison AS

更新日期：2013-02-15 00:00:00

abstract：:Ascarosides are small-molecule signals that play a central role in C. elegans biology, including dauer formation, aging, and social behaviors, but many aspects of their biosynthesis remain unknown. Using automated 2D NMR-based comparative metabolomics, we identified ascaroside ethanolamides as shunt metabolites in C. ...

journal_title：ACS chemical biology

authors： Izrayelit Y,Robinette SL,Bose N,von Reuss SH,Schroeder FC

更新日期：2013-02-15 00:00:00

abstract：:Phosphorylation-dependent protein-protein interaction has rarely been targeted in medicinal chemistry. Thymoquinone, a naturally occurring antitumor agent, disrupts prephosphorylated substrate recognition by the polo-box domain of polo-like kinase 1, a key mitotic regulator responsible for various carcinogenesis when ...

journal_title：ACS chemical biology

authors： Yin Z,Song Y,Rehse PH

更新日期：2013-02-15 00:00:00

abstract：:An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the ...

journal_title：ACS chemical biology

authors： Okamoto T,Zobel K,Fedorova A,Quan C,Yang H,Fairbrother WJ,Huang DC,Smith BJ,Deshayes K,Czabotar PE

更新日期：2013-02-15 00:00:00

abstract：:Aminoglycoside antibiotics were among the first antibiotics discovered and used clinically. Although they have never completely fallen out of favor, their importance has waned due to the emergence of other broad-spectrum antibiotics with fewer side effects. Today, with the dramatically increasing rate of infections ca...

journal_title：ACS chemical biology

authors： Becker B,Cooper MA

更新日期：2013-01-18 00:00:00

abstract：:Membrane curvature and lipid composition regulates important biological processes within a cell. Currently, several proteins have been reported to sense and/or induce membrane curvatures, e.g., Synaptotagmin-1 and Amphiphysin. However, the large protein scaffold of these curvature sensors limits their applications in ...

journal_title：ACS chemical biology

authors： Morton LA,Yang H,Saludes JP,Fiorini Z,Beninson L,Chapman ER,Fleshner M,Xue D,Yin H

更新日期：2013-01-18 00:00:00

abstract：:Rising drug resistance is limiting treatment options for infections by methicillin-resistant Staphylococcus aureus (MRSA). Herein we provide new evidence that wall teichoic acid (WTA) biogenesis is a remarkable antibacterial target with the capacity to destabilize the cooperative action of penicillin-binding proteins ...

journal_title：ACS chemical biology

authors： Farha MA,Leung A,Sewell EW,D'Elia MA,Allison SE,Ejim L,Pereira PM,Pinho MG,Wright GD,Brown ED

更新日期：2013-01-18 00:00:00

abstract：:Proteins subjected to an electric field and forced to pass through a nanopore induce blockades of ionic current that depend on the protein and nanopore characteristics and interactions between them. Recent advances in the analysis of these blockades have highlighted a variety of phenomena that can be used to study pro...

journal_title：ACS chemical biology

authors： Oukhaled A,Bacri L,Pastoriza-Gallego M,Betton JM,Pelta J

更新日期：2012-12-21 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：:Creation of an artificial oscillating gene expression system is one of the most challenging issues in synthetic biology. Here, we constructed a simple system to manipulate gene expression patterns to be circadian, reflecting the intrinsic cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc fing...

journal_title：ACS chemical biology

authors： Imanishi M,Yamamoto K,Yamada H,Hirose Y,Okamura H,Futaki S

更新日期：2012-11-16 00:00:00

abstract：:Platinum-based drugs have been used to successfully treat diverse cancers for several decades. Cisplatin, the original compound of this class, cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types, yet it exhibits toxic side effects and tumors ...

journal_title：ACS chemical biology

authors： Cheung-Ong K,Song KT,Ma Z,Shabtai D,Lee AY,Gallo D,Heisler LE,Brown GW,Bierbach U,Giaever G,Nislow C

更新日期：2012-11-16 00:00:00

abstract：:It has been known for nearly a half century that human tumors, including those derived from the nervous system such as glioblastomas, medulloblastoma, and neuroblastomas are much more sensitive than normal tissues to l-methionine (l-Met) starvation. More recently, systemic l-Met depletion by administration of Pseudomo...

journal_title：ACS chemical biology

authors： Stone E,Paley O,Hu J,Ekerdt B,Cheung NK,Georgiou G

更新日期：2012-11-16 00:00:00

abstract：:Secreted tyrosinase from melanin-forming Streptomyces avermitilis MA4680 was involved in both ortho-hydroxylation and further oxidation of trans-resveratrol, leading to the formation of melanin. This finding was confirmed by constructing deletion mutants of melC(2) and melD(2) encoding extracellular and intracellular ...

journal_title：ACS chemical biology

authors： Lee N,Kim EJ,Kim BG

更新日期：2012-10-19 00:00:00

abstract：:Ammonia lyases catalyze the formation of α,β-unsaturated bonds by the elimination of ammonia from their substrates. This conceptually straightforward reaction has been the emphasis of many studies, with the main focus on the catalytic mechanism of these enzymes and/or the use of these enzymes as catalysts for the synt...

journal_title：ACS chemical biology

authors： de Villiers M,Puthan Veetil V,Raj H,de Villiers J,Poelarends GJ

更新日期：2012-10-19 00:00:00

abstract：:MbtA is an adenylating enzyme from Mycobacterium tuberculosis that catalyzes the first step in the biosynthesis of the mycobactins. A bisubstrate inhibitor of MbtA (Sal-AMS) was previously described that displays potent antitubercular activity under iron-replete as well as iron-deficient growth conditions. This findin...

journal_title：ACS chemical biology

authors： Duckworth BP,Wilson DJ,Nelson KM,Boshoff HI,Barry CE 3rd,Aldrich CC

更新日期：2012-10-19 00:00:00

abstract：:Binding of the Fc domain of Immunoglobulin G (IgG) to Fcγ receptors on leukocytes can initiate a series of signaling events resulting in antibody-dependent cell-mediated cytotoxicity (ADCC) and other important immune responses. Fc domains lacking glycosylation at N297 have greatly diminished Fcγ receptor binding and l...

journal_title：ACS chemical biology

authors： Borrok MJ,Jung ST,Kang TH,Monzingo AF,Georgiou G

更新日期：2012-09-21 00:00:00

abstract：:The development of HIV-1 protease inhibitors has been the historic paradigm of rational structure-based drug design, where structural and thermodynamic analyses have assisted in the discovery of novel inhibitors. While the total enthalpy and entropy change upon binding determine the affinity, often the thermodynamics ...

journal_title：ACS chemical biology

authors： King NM,Prabu-Jeyabalan M,Bandaranayake RM,Nalam MN,Nalivaika EA,Özen A,Haliloğlu T,Yilmaz NK,Schiffer CA

更新日期：2012-09-21 00:00:00

abstract：:Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modifie...

journal_title：ACS chemical biology

authors： Hernández AR,Peterson LW,Kool ET

更新日期：2012-08-17 00:00:00

abstract：:Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...

journal_title：ACS chemical biology

authors： Brandvold KR,Steffey ME,Fox CC,Soellner MB

更新日期：2012-08-17 00:00:00

abstract：:Bacteria use small molecules to assess the density and identity of nearby organisms and formulate a response. This process, called quorum sensing (QS), commonly regulates bioluminescence, biofilm formation, and virulence. Vibrio harveyi have three described QS circuits. Each involves the synthesis of a molecule that r...

journal_title：ACS chemical biology

authors： Henares BM,Higgins KE,Boon EM

更新日期：2012-08-17 00:00:00

abstract：:Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 acti...

journal_title：ACS chemical biology

authors： Pollock JA,Larrea MD,Jasper JS,McDonnell DP,McCafferty DG

更新日期：2012-07-20 00:00:00

abstract：:The mitochondrial ADP/ATP carrier (AAC) is a prominent actor in the energetic regulation of the cell, importing ADP into the mitochondria and exporting ATP toward the cytoplasm. Severe genetic diseases have been ascribed to specific mutations in this membrane protein. How minute, well-localized modifications of the tr...

journal_title：ACS chemical biology

authors： Ravaud S,Bidon-Chanal A,Blesneac I,Machillot P,Juillan-Binard C,Dehez F,Chipot C,Pebay-Peyroula E

更新日期：2012-07-20 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：:The genetic code specifies 20 common amino acids and is largely preserved in both single and multicellular organisms. Unnatural amino acids (Uaas) have been genetically incorporated into proteins by using engineered orthogonal tRNA/aminoacyl-tRNA synthetase (RS) pairs, enabling new research capabilities and precision ...

journal_title：ACS chemical biology

authors： Parrish AR,She X,Xiang Z,Coin I,Shen Z,Briggs SP,Dillin A,Wang L

更新日期：2012-07-20 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：:As part of the central core domain of the ribosome, helix 69 of 23S rRNA participates in an important intersubunit bridge and contacts several protein translation factors. Helix 69 is believed to play key roles in protein synthesis. Even though high-resolution crystal structures of the ribosome exist, the solution dyn...

journal_title：ACS chemical biology

authors： Sakakibara Y,Chow CS

更新日期：2012-05-18 00:00:00

abstract：:Autophagy is a bulk, nonspecific protein degradation pathway that is involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed that xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and beer, modulates autophagy. By using XN-immobilized beads, valosin-containing...

journal_title：ACS chemical biology

authors： Sasazawa Y,Kanagaki S,Tashiro E,Nogawa T,Muroi M,Kondoh Y,Osada H,Imoto M

更新日期：2012-05-18 00:00:00

abstract：:The perturbation of protein kinases with small organic molecules is a powerful approach to dissect kinase function in complex biological systems. Covalent kinase inhibitors that target thiols in the ATP binding pocket of the kinase domain proved to be ideal reagents for the investigation of highly dynamic cellular pro...

journal_title：ACS chemical biology

authors： Koch A,Rode HB,Richters A,Rauh D,Hauf S

更新日期：2012-04-20 00:00:00

abstract：:Labeling of virus opens new pathways for the understanding of viruses themselves and facilitates the utilization of viruses in modern biology, medicine, and materials. Based on the characteristic that viruses hijack their host cellular machineries to survive and reproduce themselves, a host-cell-assisted strategy is p...

journal_title：ACS chemical biology

authors： Huang BH,Lin Y,Zhang ZL,Zhuan F,Liu AA,Xie M,Tian ZQ,Zhang Z,Wang H,Pang DW

更新日期：2012-04-20 00:00:00

abstract：:In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates to contribute new limb tissue. However, mammalian muscle cannot dedifferentiate after injury. We have developed a novel, small-molecule-based method to induce dedifferentiation in mam...

journal_title：ACS chemical biology

authors： Kim WH,Jung DW,Kim J,Im SH,Hwang SY,Williams DR

更新日期：2012-04-20 00:00:00

abstract：:Changes in glycosylation are correlated to disease and associated with differentiation processes. Experimental tools are needed to investigate the physiological implications of these changes either by labeling of the modified glycans or by blocking their biosynthesis. N-Acetylgalactosamine (GalNAc) is a monosaccharide...

journal_title：ACS chemical biology

authors： Pouilly S,Bourgeaux V,Piller F,Piller V

更新日期：2012-04-20 00:00:00

abstract：:Nature uses four methods of carbon chain elongation for the production of 2-ketoacids, fatty acids, polyketides, and isoprenoids. Using a combination of quantum mechanical (QM) modeling, protein-substrate modeling, and protein and metabolic engineering, we have engineered the enzymes involved in leucine biosynthesis f...

journal_title：ACS chemical biology

authors： Marcheschi RJ,Li H,Zhang K,Noey EL,Kim S,Chaubey A,Houk KN,Liao JC

更新日期：2012-04-20 00:00:00

abstract：:The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary comple...

journal_title：ACS chemical biology

authors： Hayashi K,Neve J,Hirose M,Kuboki A,Shimada Y,Kepinski S,Nozaki H

更新日期：2012-03-16 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：:APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput s...

journal_title：ACS chemical biology

authors： Li M,Shandilya SM,Carpenter MA,Rathore A,Brown WL,Perkins AL,Harki DA,Solberg J,Hook DJ,Pandey KK,Parniak MA,Johnson JR,Krogan NJ,Somasundaran M,Ali A,Schiffer CA,Harris RS

更新日期：2012-03-16 00:00:00

abstract：:Integrins play myriad and vital roles in development and disease. They connect a cell with its surroundings and transmit chemical and mechanical signals across the plasma membrane to the cell's interior. Dissecting their roles in cell behavior is complicated by their overlapping ligand specificity and shared downstrea...

journal_title：ACS chemical biology

authors： Klim JR,Fowler AJ,Courtney AH,Wrighton PJ,Sheridan RT,Wong ML,Kiessling LL

更新日期：2012-03-16 00:00:00

abstract：:Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR...

journal_title：ACS chemical biology

authors： Jakobsche CE,McEnaney PJ,Zhang AX,Spiegel DA

更新日期：2012-02-17 00:00:00

abstract：:The past several years have seen numerous reports of new chemical modifications for use in RNA. In addition, in that time period, we have seen the discovery of several previously unknown naturally occurring modifications that impart novel properties on the parent RNAs. In this review, we describe recent discoveries in...

journal_title：ACS chemical biology

authors： Phelps K,Morris A,Beal PA

更新日期：2012-01-20 00:00:00