abstract：:Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying ...

journal_title：ACS chemical biology

authors： Severyn B,Liehr RA,Wolicki A,Nguyen KH,Hudak EM,Ferrer M,Caldwell JS,Hermes JD,Li J,Tudor M

更新日期：2011-12-16 00:00:00

abstract：:Nephronectin is an extracellular matrix protein that interacts with the α8β1 integrin receptor and plays a role in tissue and organ development, though the motifs that mediate adhesion to the receptor remain unclear. This paper describes the use of self-assembled monolayers to study the adhesion of α8β1-presenting cel...

journal_title：ACS chemical biology

authors： Sánchez-Cortés J,Mrksich M

更新日期：2011-10-21 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 clinical application of siRNA is limited largely by the lack of efficient, cell-specific delivery systems. Antibodies are attractive delivery vehicles for targeted therapy due to their high specificity. In this study we describe the use of a humanized monoclonal antibody (mAb), hu3S193, against Lewis-Y (Le(y)), as...

journal_title：ACS chemical biology

authors： Ma Y,Kowolik CM,Swiderski PM,Kortylewski M,Yu H,Horne DA,Jove R,Caballero OL,Simpson AJ,Lee FT,Pillay V,Scott AM

更新日期：2011-09-16 00:00:00

abstract：:Chromophore-assisted light inactivation (CALI) is a potentially powerful tool for the acute disruption of a target protein inside living cells with high spatiotemporal resolution. This technology, however, has not been widely utilized, mainly because of the lack of an efficient chromophore as the photosensitizing agen...

journal_title：ACS chemical biology

authors： Takemoto K,Matsuda T,McDougall M,Klaubert DH,Hasegawa A,Los GV,Wood KV,Miyawaki A,Nagai T

更新日期：2011-05-20 00:00:00

abstract：:To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of...

journal_title：ACS chemical biology

authors： Strittmatter T,Bareth B,Immel TA,Huhn T,Mayer TU,Marx A

更新日期：2011-04-15 00:00:00

abstract：:The display and analysis of proteins expressed on biological surfaces has become an attractive tool for the study of molecular interactions in enzymology, protein engineering, and high-throughput screening. Among the growing number of established display systems, retroviruses offer a unique and fully mammalian platfor...

journal_title：ACS chemical biology

authors： Urban JH,Merten CA

更新日期：2011-01-21 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：:The limited clinical success of therapeutics targeting cellular signaling processes is due to multiple factors, including off-target effects and complex feedback regulation encoded within the signaling network. To understand these effects, chemical proteomics and chemical genetics tools have been developed to map the ...

journal_title：ACS chemical biology

authors： Carlson SM,White FM

更新日期：2011-01-21 00:00:00

abstract：:Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (...

journal_title：ACS chemical biology

authors： Nelson JW,Chamessian AG,McEnaney PJ,Murelli RP,Kazmierczak BI,Spiegel DA

更新日期：2010-12-17 00:00:00

abstract：:In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nu...

journal_title：ACS chemical biology

authors： Hintersteiner M,Ambrus G,Bednenko J,Schmied M,Knox AJ,Meisner NC,Gstach H,Seifert JM,Singer EL,Gerace L,Auer M

更新日期：2010-10-15 00:00:00

abstract：:Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates o...

journal_title：ACS chemical biology

authors： Bolognesi B,Kumita JR,Barros TP,Esbjorner EK,Luheshi LM,Crowther DC,Wilson MR,Dobson CM,Favrin G,Yerbury JJ

更新日期：2010-08-20 00:00:00

abstract：:The ubiquity of microorganisms is unparalleled in any other known organism. These creatures surround our outsides and colonize our insides, a fact that has been known for centuries. However, despite their prevalence and long study, many of their characteristics still remain largely unexplained, including how proteins ...

journal_title：ACS chemical biology

authors： Brownlee C

更新日期：2010-07-16 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：: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：:Clostridium difficile, a leading cause of hospital-acquired infection, possesses a dense surface layer (S-layer) that mediates host-pathogen interactions. The key structural components of the S-layer result from proteolytic cleavage of a precursor protein, SlpA, into high- and low-molecular-weight components. Here we ...

journal_title：ACS chemical biology

authors： Dang TH,de la Riva L,Fagan RP,Storck EM,Heal WP,Janoir C,Fairweather NF,Tate EW

更新日期：2010-03-19 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：: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：:Chemical synthesis is a powerful method for precise modification of the structural and electronic properties of proteins. The difficulties in the synthesis and purification of peptides containing transmembrane segments have presented obstacles to the chemical synthesis of integral membrane proteins. Here, we present a...

journal_title：ACS chemical biology

authors： Komarov AG,Linn KM,Devereaux JJ,Valiyaveetil FI

更新日期：2009-12-18 00:00:00

abstract：:The nematode Caenorhabditis elegans is an excellent model organism for studies of glycan dynamics, a goal that requires tools for imaging glycans in vivo. Here we applied the bioorthogonal chemical reporter technique for the molecular imaging of mucin-type O-glycans in live C. elegans. We treated worms with azidosugar...

journal_title：ACS chemical biology

authors： Laughlin ST,Bertozzi CR

更新日期：2009-12-18 00:00:00

abstract：:Understanding the ways in which pathogens invade and neutralize their hosts is of great interest from both an academic and a clinical perspective. However, in many cases genetic tools are unavailable or insufficient to fully characterize the detailed mechanisms of pathogenesis. Small molecule approaches are particular...

journal_title：ACS chemical biology

authors： Puri AW,Bogyo M

更新日期：2009-08-21 00:00:00

abstract：:ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tis...

journal_title：ACS chemical biology

authors： Henrich CJ,Robey RW,Takada K,Bokesch HR,Bates SE,Shukla S,Ambudkar SV,McMahon JB,Gustafson KR

更新日期：2009-08-21 00:00:00

abstract：:How primitive enzymes emerged from a primordial pool remains a fundamental unanswered question with important practical implications in synthetic biology. Here we show that a de novo evolved ATP binding protein, selected solely on the basis of its ability to bind ATP, mediates the regiospecific hydrolysis of ATP to AD...

journal_title：ACS chemical biology

authors： Simmons CR,Stomel JM,McConnell MD,Smith DA,Watkins JL,Allen JP,Chaput JC

更新日期：2009-08-21 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：:Beta-peptides (beta-amino acid oligomers) that mimic the amphiphilic, helical, and cationic properties of natural antimicrobial peptides have previously been shown to display antifungal activity against planktonic Candida albicans cells. Beta-peptides offer several advantages over conventional peptides composed of alp...

journal_title：ACS chemical biology

authors： Karlsson AJ,Pomerantz WC,Neilsen KJ,Gellman SH,Palecek SP

更新日期：2009-07-17 00:00:00

abstract：:Fatty acylation or lipid modification of proteins controls their cellular activation and diverse roles in physiology. It mediates protein-protein and protein-membrane interactions and plays an important role in regulating cellular signaling pathways. Currently, there is need for visualizing lipid modifications of prot...

journal_title：ACS chemical biology

authors： Hannoush RN,Arenas-Ramirez N

更新日期：2009-07-17 00:00:00

abstract：:Combinatorial libraries built with severely restricted chemical diversity have yielded highly functional synthetic binding proteins. Structural analyses of these minimalist binding sites have revealed the dominant role of large tyrosine residues for mediating molecular contacts and of small serine/glycine residues for...

journal_title：ACS chemical biology

authors： Koide S,Sidhu SS

更新日期：2009-05-15 00:00:00

abstract：:Plasmodium falciparum thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in folate biosynthesis and a major malarial drug target. This bifunctional enzyme thus presents different design approaches for developing novel inhibitors against drug-resistant mutants. We performed a high-throughput ...

journal_title：ACS chemical biology

authors： Dasgupta T,Chitnumsub P,Kamchonwongpaisan S,Maneeruttanarungroj C,Nichols SE,Lyons TM,Tirado-Rives J,Jorgensen WL,Yuthavong Y,Anderson KS

更新日期：2009-01-16 00:00:00

abstract：:Agonists and antagonists of the nicotinic acetylcholine receptor (nAChR) are used to treat nicotine addiction, neuromuscular disorders, and neurological diseases. In designing small molecule therapeutics with the nAChR as a target, it is useful to identify chemical parameters that correlate with ability to activate th...

journal_title：ACS chemical biology

authors： Tantama M,Licht S

更新日期：2008-11-21 00:00:00

abstract：:Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene, which produces an essential protein known as SMN. The severity of SMA is modified by variable copy number of a second gene,SMN2, which produces an mRNA that is incorrectly spliced with deletion of the last exon. We describ...

journal_title：ACS chemical biology

authors： Singh J,Salcius M,Liu SW,Staker BL,Mishra R,Thurmond J,Michaud G,Mattoon DR,Printen J,Christensen J,Bjornsson JM,Pollok BA,Kiledjian M,Stewart L,Jarecki J,Gurney ME

更新日期：2008-11-21 00:00:00

abstract：:Glycosylphosphatidylinositol (GPI)-anchored proteins are abundant in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness in humans and the related disease Nagana in cattle, and disruption of GPI biosynthesis is genetically and chemically validated as a drug target. Here, we exam...

journal_title：ACS chemical biology

authors： Urbaniak MD,Yashunsky DV,Crossman A,Nikolaev AV,Ferguson MA

更新日期：2008-10-17 00:00:00

abstract：:Regulation of gene expression by RNA processing mechanisms is now understood to be an important level of control in mammalian cells. Regulation at the level of RNA transcription, splicing, polyadenylation, nucleo-cytoplasmic transport, and translation into polypeptides has been well-studied. Alternative RNA processing...

journal_title：ACS chemical biology

authors： Lutz CS

更新日期：2008-10-17 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：:Peptidoglycan glycosyltransferases (PGTs), enzymes that catalyze the formation of the glycan chains of the bacterial cell wall, have tremendous potential as antibiotic targets. The moenomycins, a potent family of natural product antibiotics, are the only known active site inhibitors of the PGTs and serve as blueprints...

journal_title：ACS chemical biology

authors： Yuan Y,Fuse S,Ostash B,Sliz P,Kahne D,Walker S

更新日期：2008-07-18 00:00:00

abstract：:Mutations that constitutively activate the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, including alterations in PI3K, PTEN, and AKT, are found in a variety of human cancers, implicating the PI3K lipid kinase as an attractive target for the development of therapeutic agents to treat cancer and other relate...

journal_title：ACS chemical biology

authors： Xie P,Williams DS,Atilla-Gokcumen GE,Milk L,Xiao M,Smalley KS,Herlyn M,Meggers E,Marmorstein R

更新日期：2008-05-16 00:00:00

abstract：:There is increasing concern that animal and human reproduction may be adversely affected by exposure to xenoestrogens that activate estrogen receptors. There is evidence that one such compound, Bisphenol A (BPA), also induces meiotic and mitotic aneuploidy, suggesting that these kinds of molecules may also have effect...

journal_title：ACS chemical biology

authors： George O,Bryant BK,Chinnasamy R,Corona C,Arterburn JB,Shuster CB

更新日期：2008-03-20 00:00:00

abstract：:Polyalkoxybenzenes are plant components displaying a wide range of biological activities. In these studies, we synthesized apiol and dillapiol isoxazoline analogues of combretastatins and evaluated their effect on sea urchin embryos. We have shown that p-methoxyphenyl isoxazoline caused sea urchin embryo immobilizatio...

journal_title：ACS chemical biology

authors： Semenova MN,Tsyganov DV,Yakubov AP,Kiselyov AS,Semenov VV

更新日期：2008-02-15 00:00:00

abstract：:Synthetic biology is the realization of systems with desired behavior using biological materials. A recent addition to the field is a bipartite consortium of the bacterium Escherichia coli in which each species harbors complementary gene circuits that actuate only when both are present above a critical density. This b...

journal_title：ACS chemical biology

authors： Wong JV,Song H,You L

更新日期：2008-01-18 00:00:00

abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...

journal_title：ACS chemical biology

authors： de Paz JL,Moseman EA,Noti C,Polito L,von Andrian UH,Seeberger PH

更新日期：2007-11-20 00:00:00

abstract：:There is a pressing need for new molecular tools to target protein surfaces with high affinity and specificity. Here, we describe cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library. Using this library, we have designed a number of high-affinity, redox-insensitive, cyclic peptides t...

journal_title：ACS chemical biology

authors： Millward SW,Fiacco S,Austin RJ,Roberts RW

更新日期：2007-09-21 00:00:00