Structure-based design of an organoruthenium phosphatidyl-inositol-3-kinase inhibitor reveals a switch governing lipid kinase potency and selectivity.

abstract：:Protein organization on biomembranes and their dynamics are essential for cellular function. It is not clear, however, how protein binding may influence the assembly of underlying lipids or how the membrane structure leads to functional protein organization. Toward this goal, we investigated the effects of annexin a5 ...

journal_title：ACS chemical biology

authors： Vats K,Knutson K,Hinderliter A,Sheets ED

更新日期：2010-04-16 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：:Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical l...

journal_title：ACS chemical biology

authors： Ranganathan A,Heine P,Rudling A,Plückthun A,Kummer L,Carlsson J

更新日期：2017-03-17 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：:Stapled peptides have great potential as modulators of protein-protein interactions (PPIs). However, there is a vast landscape of chemical features that can be varied for any given peptide, and identifying a set of features that maximizes cellular uptake and subsequent target engagement remains a key challenge. Herein...

journal_title：ACS chemical biology

authors： Wu Y,Kaur A,Fowler E,Wiedmann MM,Young R,Galloway WRJD,Olsen L,Sore HF,Chattopadhyay A,Kwan TT,Xu W,Walsh SJ,de Andrade P,Janecek M,Arumugam S,Itzhaki LS,Lau YH,Spring DR

更新日期：2019-03-15 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：: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：:For the specificity of ALOX15 orthologs of different mammals, the geometry of the amino acids Phe353, Ile418, Met419, and Ile593 ("triad determinants") is important, and mutagenesis of these residues altered the reaction specificity of these enzymes. Here we expressed wild-type human ALOX5 and its F359W/A424I/N425M/A6...

journal_title：ACS chemical biology

authors： Ivanov I,Golovanov AB,Ferretti C,Canyelles-Niño M,Heydeck D,Stehling S,Lluch JM,González-Lafont À,Kühn H

更新日期：2019-12-20 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：:This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli bu...

journal_title：ACS chemical biology

authors： Wang G,Hanke ML,Mishra B,Lushnikova T,Heim CE,Chittezham Thomas V,Bayles KW,Kielian T

更新日期：2014-09-19 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：: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：: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：:The innate immune system provides the first line of defense against pathogens through the recognition of nonspecific patterns in RNA to protect the cell in a generalized way. The human RNA-activated protein kinase, PKR, is a dsRNA binding protein and an essential sensor in the innate immune response, which recognizes ...

journal_title：ACS chemical biology

authors： Hull CM,Anmangandla A,Bevilacqua PC

更新日期：2016-04-15 00:00:00

abstract：:Drug resistance continues to be a growing global problem. The efficacy of small molecule inhibitors is threatened by pools of genetic diversity in all systems, including antibacterials, antifungals, cancer therapeutics, and antivirals. Resistant variants often include combinations of active site mutations and distal "...

journal_title：ACS chemical biology

authors： Henes M,Lockbaum GJ,Kosovrasti K,Leidner F,Nachum GS,Nalivaika EA,Lee SK,Spielvogel E,Zhou S,Swanstrom R,Bolon DNA,Kurt Yilmaz N,Schiffer CA

更新日期：2019-11-15 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：: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：:Diversity of scaffold structure and function is a hallmark of the >50,000 isoprenoid natural products such as taxol. Whereas most members of this class are assembled by iterative head-to-tail enzymatic joining reactions between delta2- and delta3-isopentenyl diphosphate (IPP) monomers, dimerization of two delta2-IPP m...

journal_title：ACS chemical biology

authors： Walsh CT

更新日期：2007-05-22 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：: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：:The Bcl-2 family of proteins is crucial for apoptosis regulation. Members of this family insert through a specific C-terminal anchoring transmembrane domain (TMD) in the mitochondrial outer membrane where they hierarchically interact to determine cell fate. While the mitochondrial membrane has been proposed to activel...

journal_title：ACS chemical biology

authors： Andreu-Fernández V,Genoves A,Lee TH,Stellato M,Lucantoni F,Orzáez M,Mingarro I,Aguilar MI,Pérez-Payá E

更新日期：2014-08-15 00:00:00

abstract：:KCNE transmembrane peptides are a family of modulatory beta-subunits that assemble with voltage-gated K+ channels, producing the diversity of potassium currents needed for proper function in a variety of tissues. Although all five KCNE transcripts have been found in cardiac and other tissues, it is unclear whether two...

journal_title：ACS chemical biology

authors： Morin TJ,Kobertz WR

更新日期：2007-07-20 00:00:00

abstract：:The expansion of the genetic code with noncanonical amino acids (ncAA) enables the function of proteins to be tailored with high molecular precision. In this approach, the ncAA is charged to an orthogonal nonsense suppressor tRNA by an aminoacyl-tRNA-synthetase (aaRS) and incorporated into the target protein in vivo b...

journal_title：ACS chemical biology

authors： Pott M,Schmidt MJ,Summerer D

更新日期：2014-12-19 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：:Light-activated protein domains provide a convenient, modular, and genetically encodable sensor for optogenetics and optobiology. Although these domains have now been deployed in numerous systems, the precise mechanism of photoactivation and the accompanying structural dynamics that modulate output domain activity rem...

journal_title：ACS chemical biology

authors： Iuliano JN,Collado JT,Gil AA,Ravindran PT,Lukacs A,Shin S,Woroniecka HA,Adamczyk K,Aramini JM,Edupuganti UR,Hall CR,Greetham GM,Sazanovich IV,Clark IP,Daryaee T,Toettcher JE,French JB,Gardner KH,Simmerling CL,Meech

更新日期：2020-10-16 00:00:00

abstract：:The inhibitor of apoptosis (IAP) proteins are critical regulators of cancer cell survival, which makes them attractive targets for therapeutic intervention in cancers. Herein, we describe the structure-based design of IAP antagonists with high affinities and selectivity (>2000-fold) for c-IAP1 over XIAP and their func...

journal_title：ACS chemical biology

authors： Ndubaku C,Varfolomeev E,Wang L,Zobel K,Lau K,Elliott LO,Maurer B,Fedorova AV,Dynek JN,Koehler M,Hymowitz SG,Tsui V,Deshayes K,Fairbrother WJ,Flygare JA,Vucic D

更新日期：2009-07-17 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：:Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epig...

journal_title：ACS chemical biology

authors： Maurer S,Giess M,Koch O,Summerer D

更新日期：2016-12-16 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：: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