YTHDF2 Recognition of N1-Methyladenosine (m1A)-Modified RNA Is Associated with Transcript Destabilization.

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：:The canonical NF-κB signaling pathway is a mediator of the cellular inflammatory response and a target for developing therapeutics for multiple human diseases. The furthest downstream proteins in the pathway, the p50/p65 transcription factor heterodimer, have been recalcitrant toward small molecule inhibition despite ...

journal_title：ACS chemical biology

authors： Widen JC,Kempema AM,Villalta PW,Harki DA

更新日期：2017-01-20 00:00:00

abstract：:RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor pro...

journal_title：ACS chemical biology

authors： Assimon VA,Tang Y,Vargas JD,Lee GJ,Wu ZY,Lou K,Yao B,Menon MK,Pios A,Perez KC,Madriaga A,Buchowiecki PK,Rolfe M,Shawver L,Jiao X,Le Moigne R,Zhou HJ,Anderson DJ

更新日期：2019-02-15 00:00:00

abstract：:Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for...

journal_title：ACS chemical biology

authors： Ohana RF,Kirkland TA,Woodroofe CC,Levin S,Uyeda HT,Otto P,Hurst R,Robers MB,Zimmerman K,Encell LP,Wood KV

更新日期：2015-10-16 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：:The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising and clinically unexploited antibiotic targets for treatment of multidrug-resistant Gram-negative infections. Progress in medicinal chemistry has led to the discovery of potent LpxC inhibitors with a variety of chemical scaffolds and disti...

journal_title：ACS chemical biology

authors： Lee CJ,Liang X,Gopalaswamy R,Najeeb J,Ark ED,Toone EJ,Zhou P

更新日期：2014-01-17 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：: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：:New machine learning methods to analyze raw chemical and biological data are now widely accessible as open-source toolkits. This positions researchers to leverage powerful, predictive models in their own domains. We caution, however, that the application of machine learning to experimental research merits careful cons...

journal_title：ACS chemical biology

authors： Chuang KV,Keiser MJ

更新日期：2018-10-19 00:00:00

abstract：:The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...

journal_title：ACS chemical biology

authors： Cullen A,D'Agostino PM,Mazmouz R,Pickford R,Wood S,Neilan BA

更新日期：2018-11-16 00:00:00

abstract：:The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

journal_title：ACS chemical biology

authors： Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

更新日期：2017-12-15 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：:Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene ex...

journal_title：ACS chemical biology

authors： Deochand DK,Meariman JK,Grove A

更新日期：2016-07-15 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：: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：:A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...

journal_title：ACS chemical biology

authors： Sharma A,Toy W,Guillen VS,Sharma N,Min J,Carlson KE,Mayne CG,Lin S,Sabio M,Greene G,Katzenellenbogen BS,Chandarlapaty S,Katzenellenbogen JA

更新日期：2018-12-21 00:00:00

abstract：:The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociati...

journal_title：ACS chemical biology

authors： Bjelic S,Nivón LG,Çelebi-Ölçüm N,Kiss G,Rosewall CF,Lovick HM,Ingalls EL,Gallaher JL,Seetharaman J,Lew S,Montelione GT,Hunt JF,Michael FE,Houk KN,Baker D

更新日期：2013-04-19 00:00:00

abstract：:Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...

journal_title：ACS chemical biology

authors： Tang X,Zhang F,Zeng T,Li W,Yin S,Wu R

更新日期：2020-10-16 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：: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：:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive pro...

journal_title：ACS chemical biology

authors： Childs-Disney JL,Disney MD

更新日期：2016-02-19 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：:RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In t...

journal_title：ACS chemical biology

authors： Schapira M

更新日期：2016-03-18 00:00:00

abstract：:Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in a...

journal_title：ACS chemical biology

authors： Battersby BJ,Richter U,Safronov O

更新日期：2019-11-15 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：:Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, the causative agents of severe malaria and toxoplasmosis, respectively, undergo several critical developmental transitions during their lifecycle. Most important for human pathogenesis is the asexual cycle, in which parasites undergo rounds...

journal_title：ACS chemical biology

authors： Howard BL,Harvey KL,Stewart RJ,Azevedo MF,Crabb BS,Jennings IG,Sanders PR,Manallack DT,Thompson PE,Tonkin CJ,Gilson PR

更新日期：2015-04-17 00:00:00

abstract：:Desferrioxamine B (DFOB) was discovered in the late 1950s as a hydroxamic acid metabolite of the soil bacterium Streptomyces pilosus. The exquisite affinity of DFOB for Fe(III) identified its potential for removing excess iron from patients with transfusion-dependent hemoglobin disorders. Many studies have used semisy...

journal_title：ACS chemical biology

authors： Codd R,Richardson-Sanchez T,Telfer TJ,Gotsbacher MP

更新日期：2018-01-19 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：:Histone post-translational modifications (PTMs) are crucial for many cellular processes including mitosis, transcription, and DNA repair. The cellular readout of histone PTMs is dependent on both the chemical modification and histone site, and the array of histone PTMs on chromatin is dynamic throughout the eukaryotic...

journal_title：ACS chemical biology

authors： Albanese KI,Krone MW,Petell CJ,Parker MM,Strahl BD,Brustad EM,Waters ML

更新日期：2020-01-17 00:00:00

abstract：:The degree to which anticancer agents selectively target cancer cells is a key determinant in successful therapeutic outcomes. Inhibitors of the Hsp90 molecular chaperone represent an important new class of anticancer agents. We propose here a novel mechanism by which physiochemical properties of Hsp90 inhibitors can ...

journal_title：ACS chemical biology

authors： Duvvuri M,Konkar S,Hong KH,Blagg BS,Krise JP

更新日期：2006-06-20 00:00:00