Activation of the NLRP3 Inflammasome by Hyaboron, a New Asymmetric Boron-Containing Macrodiolide from the Myxobacterium Hyalangium minutum.

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：:SGK3 is a PX domain containing protein kinase activated at endosomes downstream of class 1 and 3 PI3K family members by growth factors and oncogenic mutations. SGK3 plays a key role in mediating resistance of breast cancer cells to class 1 PI3K or Akt inhibitors, by substituting for the loss of Akt activity and restor...

journal_title：ACS chemical biology

authors： Tovell H,Testa A,Zhou H,Shpiro N,Crafter C,Ciulli A,Alessi DR

更新日期：2019-09-20 00:00:00

abstract：:Detection of metabolites and post-translational modifications can be achieved using the azide as a bioorthogonal chemical reporter. Once introduced into target biomolecules, either metabolically or through chemical modification, the azide can be tagged with probes using one of three highly selective reactions: the Sta...

journal_title：ACS chemical biology

authors： Agard NJ,Baskin JM,Prescher JA,Lo A,Bertozzi CR

更新日期：2006-11-21 00:00:00

abstract：:The arabinosyltransferases responsible for the biosynthesis of the arabinan domains of two abundant heteropolysaccharides of the cell envelope of all mycobacterial species, lipoarabinomannan and arabinogalactan, are validated drug targets. Using a cell envelope preparation from Mycobacterium smegmatis as the enzyme so...

journal_title：ACS chemical biology

authors： Angala SK,McNeil MR,Zou L,Liav A,Zhang J,Lowary TL,Jackson M

更新日期：2016-06-17 00:00:00

abstract：:Unrelated ligands, often found in drug discovery campaigns, can bind to the same receptor, even with the same protein residues. To investigate how this might occur, and whether it might be typically possible to find unrelated ligands for the same drug target, we sought examples of topologically unrelated ligands that ...

journal_title：ACS chemical biology

authors： Pottel J,Levit A,Korczynska M,Fischer M,Shoichet BK

更新日期：2018-09-21 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：: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：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...

journal_title：ACS chemical biology

authors： Qin K,Zhu Y,Qin W,Gao J,Shao X,Wang YL,Zhou W,Wang C,Chen X

更新日期：2018-08-17 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：:miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have d...

journal_title：ACS chemical biology

authors： Bose D,Jayaraj GG,Kumar S,Maiti S

更新日期：2013-05-17 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：: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：: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：:Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex pr...

journal_title：ACS chemical biology

authors： Unudurthi SD,Hotta K,Kim CY

更新日期：2013-11-15 00:00:00

abstract：:The heat shock response is an evolutionarily conserved, stress-responsive signaling pathway that adapts cellular proteostasis in response to pathologic insult. In metazoans, the heat shock response primarily functions through the posttranslational activation of heat shock factor 1 (HSF1), a stress-responsive transcrip...

journal_title：ACS chemical biology

authors： Ryno LM,Genereux JC,Naito T,Morimoto RI,Powers ET,Shoulders MD,Wiseman RL

更新日期：2014-06-20 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 molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically,...

journal_title：ACS chemical biology

authors： Hall JA,Kusuma BR,Brandt GE,Blagg BS

更新日期：2014-04-18 00:00:00

abstract：:A complication of diabetes is the inability of wounds to heal in diabetic patients. Diabetic wounds are refractory to healing due to the involvement of activated matrix metalloproteinases (MMPs), which remodel the tissue resulting in apoptosis. There are no readily available methods that identify active unregulated MM...

journal_title：ACS chemical biology

authors： Gooyit M,Peng Z,Wolter WR,Pi H,Ding D,Hesek D,Lee M,Boggess B,Champion MM,Suckow MA,Mobashery S,Chang M

更新日期：2014-01-17 00:00:00

abstract：:Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...

journal_title：ACS chemical biology

authors： Bashore C,Jaishankar P,Skelton NJ,Fuhrmann J,Hearn BR,Liu PS,Renslo AR,Dueber EC

更新日期：2020-06-19 00:00:00

abstract：:WS9326A and annimycin are produced by Streptomyces asterosporus DSM 41452. WS9326A is a nonribosomal peptide synthetase-(NRPS-) derived depsipeptide containing a cinnamoyl moiety, while annimycin is a linear polyketide bearing a 2-amino-3-hydroxycyclopent-2-enone (C5N) group. Both gene clusters have been sequenced and...

journal_title：ACS chemical biology

authors： Zhu J,Zhang S,Zechel DL,Paululat T,Bechthold A

更新日期：2019-08-16 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：: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：: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：:The epidermal growth-factor-like domain A (EGF-A) of the low-density lipoprotein (LDL) receptor is a promising lead for therapeutic inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the clinical potential of EGF-A is limited by its suboptimal affinity for PCSK9. Here, we use phage display t...

journal_title：ACS chemical biology

authors： Tombling BJ,Lammi C,Lawrence N,Li J,Arnoldi A,Craik DJ,Wang CK

更新日期：2021-01-29 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：: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：: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：:Small molecules that bind to voltage-gated sodium channels (VGSCs) are promising leads in the treatment of numerous neurodegenerative diseases and pain. Nature is a highly skilled medicinal chemist in this regard, designing potent VGSC ligands capable of binding to and blocking the channel, thereby offering compounds ...

journal_title：ACS chemical biology

authors： Lukowski AL,Denomme N,Hinze ME,Hall S,Isom LL,Narayan ARH

更新日期：2019-05-17 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：:We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed f...

journal_title：ACS chemical biology

authors： Prakash TP,Lima WF,Murray HM,Elbashir S,Cantley W,Foster D,Jayaraman M,Chappell AE,Manoharan M,Swayze EE,Crooke ST

更新日期：2013-07-19 00:00:00