A chemical genetic approach for covalent inhibition of analogue-sensitive aurora kinase.

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：:Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both i...

journal_title：ACS chemical biology

authors： Hodge CD,Edwards RA,Markin CJ,McDonald D,Pulvino M,Huen MS,Zhao J,Spyracopoulos L,Hendzel MJ,Glover JN

更新日期：2015-07-17 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：: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：:Chemical genetics is a powerful approach for identifying therapeutically active small molecules, but identifying the mechanisms of action underlying hit compounds remains challenging. Chemoproteomic platforms have arisen to tackle this challenge and enable rapid mechanistic deconvolution of small-molecule screening hi...

journal_title：ACS chemical biology

authors： Counihan JL,Wiggenhorn AL,Anderson KE,Nomura DK

更新日期：2018-08-17 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：:Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significan...

journal_title：ACS chemical biology

authors： Moon K,Xu F,Zhang C,Seyedsayamdost MR

更新日期：2019-04-19 00:00:00

abstract：:Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...

journal_title：ACS chemical biology

authors： Vannecke W,Ampe C,Van Troys M,Beltramo M,Madder A

更新日期：2017-08-18 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：: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：:This report highlights the advantages of low-affinity, multivalent interactions to recognize one cell type over another. Our goal was to devise a strategy to mediate selective killing of tumor cells, which are often distinguished from normal cells by their higher levels of particular cell surface receptors. To test wh...

journal_title：ACS chemical biology

authors： Carlson CB,Mowery P,Owen RM,Dykhuizen EC,Kiessling LL

更新日期：2007-02-20 00:00:00

abstract：:There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug ...

journal_title：ACS chemical biology

authors： Arencibia JM,Fröhner W,Krupa M,Pastor-Flores D,Merker P,Oellerich T,Neimanis S,Schmithals C,Köberle V,Süß E,Zeuzem S,Stark H,Piiper A,Odadzic D,Schulze JO,Biondi RM

更新日期：2017-02-17 00:00:00

abstract：:The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the B...

journal_title：ACS chemical biology

authors： Miller TC,Rutherford TJ,Birchall K,Chugh J,Fiedler M,Bienz M

更新日期：2014-12-19 00:00:00

abstract：:Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread application and development as a drug. Here, we report the identification of Streptomyces sp. S816, isolated from Philippine man...

journal_title：ACS chemical biology

authors： Zhou S,Song L,Masschelein J,Sumang FAM,Papa IA,Zulaybar TO,Custodio AB,Zabala D,Alcantara EP,de Los Santos ELC,Challis GL

更新日期：2019-06-21 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：:A major goal of personalized medicine in oncology is the identification of drugs with predictable efficacy based on a specific trait of the cancer cell, as has been demonstrated with gleevec (presence of Bcr-Abl protein), herceptin (Her2 overexpression), and iressa (presence of a specific EGFR mutation). This is a cha...

journal_title：ACS chemical biology

authors： Parkinson EI,Bair JS,Cismesia M,Hergenrother PJ

更新日期：2013-10-18 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：: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：:We report here an isatin derivative 45 (ID45) against coxsackievirus B3 (CVB3) replication, which was synthesized based on a high-throughput screen of a unique natural product library. ID45 showed the most potent anti-CVB3 activity among the four synthesized compounds. Treatment of cells with ID45 before or after infe...

journal_title：ACS chemical biology

authors： Zhang HM,Dai H,Hanson PJ,Li H,Guo H,Ye X,Hemida MG,Wang L,Tong Y,Qiu Y,Liu S,Wang F,Song F,Zhang B,Wang JG,Zhang LX,Yang D

更新日期：2014-04-18 00:00:00

abstract：:Modern visualization techniques are affording a peek into complex cellular processes. A recent paper describes an automated fluorescence microscopy method to map the subcellular localization of up to 100 different proteins in the same sample. ...

journal_title：ACS chemical biology

authors： Jacquier V,Michnick SW

更新日期：2006-12-15 00:00:00

abstract：:Developing computational tools for a chassis-centered biosynthetic pathway design is very important for a productive heterologous biosynthesis system by considering enormous foreign biosynthetic reactions. For many cases, a pathway to produce a target molecule consists of both native and heterologous reactions when ut...

journal_title：ACS chemical biology

authors： Ding S,Liao X,Tu W,Wu L,Tian Y,Sun Q,Chen J,Hu QN

更新日期：2017-11-17 00:00:00

abstract：:The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...

journal_title：ACS chemical biology

authors： Nett RS,Contreras T,Peters RJ

更新日期：2017-04-21 00:00:00

abstract：:Photoinduced cross-linking (PIC) has become a powerful tool in chemical biology for the identification and mapping of stable or transient interactions between biomacromolecules and their (unknown) ligands. However, the value of PIC for in vitro and in vivo structural proteomics can be realized only if cross-linking re...

journal_title：ACS chemical biology

authors： Preston GW,Radford SE,Ashcroft AE,Wilson AJ

更新日期：2014-03-21 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：:Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investig...

journal_title：ACS chemical biology

authors： Ho PI,Yue K,Pandey P,Breault L,Harbinski F,McBride AJ,Webb B,Narahari J,Karassina N,Wood KV,Hill A,Auld DS

更新日期：2013-05-17 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：:Inducible modulation is often required for precise investigations and manipulations of dynamic biological processes. Transcription activator-like effectors (TALEs) provide a powerful tool for targeted gene editing and transcriptional programming. We designed a series of chemical inducible systems by coupling TALEs wit...

journal_title：ACS chemical biology

authors： Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Y

更新日期：2018-03-16 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：: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：:Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in h...

journal_title：ACS chemical biology

authors： Barr D,Szennyes E,Bokor É,Al-Oanzi ZH,Moffatt C,Kun S,Docsa T,Sipos Á,Davies MP,Mathomes RT,Snape TJ,Agius L,Somsák L,Hayes JM

更新日期：2019-07-19 00:00:00