Chemistry & biology最新文献_第8页

Metal Ion-Mediated Nucleobase Recognition by the ZTP Riboswitch. 金属离子介导的ZTP核开关核碱基识别。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-07-02 DOI: 10.1016/j.chembiol.2015.06.007

Jeremiah J Trausch, Joan G Marcano-Velázquez, Michal M Matyjasik, Robert T Batey

引用次数: 43

Increasing the Diversity of Known Pictet-Spenglerases. 增加已知pictet - spenglerase的多样性。

Chemistry & biology Pub Date : 2015-07-23 DOI: 10.1016/j.chembiol.2015.07.003

Martin E Tanner

引用次数: 4

Modularity of RiPP Enzymes Enables Designed Synthesis of Decorated Peptides. RiPP酶的模块化使设计合成修饰肽成为可能。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-07-09 DOI: 10.1016/j.chembiol.2015.06.014

Debosmita Sardar, Zhenjian Lin, Eric W Schmidt

{"title":"Modularity of RiPP Enzymes Enables Designed Synthesis of Decorated Peptides.","authors":"Debosmita Sardar, Zhenjian Lin, Eric W Schmidt","doi":"10.1016/j.chembiol.2015.06.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.014","url":null,"abstract":"Macrocyclases and other posttranslational enzymes afford derived peptides with improved properties for pharmaceutical and biotechnological applications. Here, we asked whether multiple posttranslational modifications could be simultaneously controlled and matched to rationally generate new peptide derivatives. We reconstituted the cyanobactin peptide natural products in vitro with up to five different posttranslational enzymes in a single tube. By manipulating the order of addition and identity of enzymes and exploiting their broad-substrate tolerance, we engineered the production of highly unnatural derivatives, including an N-C peptide macrocycle of 22 amino acids in length. In addition to engineering, this work better defines the macrocyclization mechanism, provides the first biochemical demonstration of Ser/Thr posttranslational prenylation, and is the first example of reconstitution of a native, multistep RiPP pathway with multiple enzymes in one pot. Overall, this work demonstrates how the modularity of posttranslational modification enzymes can be used to design and synthesize desirable peptide motifs.","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"907-16"},"PeriodicalIF":0.0,"publicationDate":"2015-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34280755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 65

Nuclear Localization and Gene Expression Modulation by a Fluorescent Sequence-Selective p-Anisyl-benzimidazolecarboxamido Imidazole-Pyrrole Polyamide. 一种具有荧光序列选择性的对苯甲酰基苯并咪唑甲酰胺咪唑-吡咯聚酰胺的核定位和基因表达调控。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-06-25 DOI: 10.1016/j.chembiol.2015.06.005

Konstantinos Kiakos, Luke Pett, Vijay Satam, Pravin Patil, Daniel Hochhauser, Moses Lee, John A Hartley

{"title":"Nuclear Localization and Gene Expression Modulation by a Fluorescent Sequence-Selective p-Anisyl-benzimidazolecarboxamido Imidazole-Pyrrole Polyamide.","authors":"Konstantinos Kiakos, Luke Pett, Vijay Satam, Pravin Patil, Daniel Hochhauser, Moses Lee, John A Hartley","doi":"10.1016/j.chembiol.2015.06.005","DOIUrl":"10.1016/j.chembiol.2015.06.005","url":null,"abstract":"Synthetic pyrrole (P)-imidazole (I) containing polyamides can target predetermined DNA sequences and modulate gene expression by interfering with transcription factor binding. We have previously shown that rationally designed polyamides targeting the inverted CCAAT box 2 (ICB2) of the topoisomerase IIα (topo IIα) promoter can inhibit binding of transcription factor NF-Y, re-inducing expression of the enzyme in confluent cells. Here, the A/T recognizing fluorophore, p-anisylbenzimidazolecarboxamido (Hx) was incorporated into the hybrid polyamide HxIP, which fluoresces upon binding to DNA, providing an intrinsic probe to monitor cellular uptake. HxIP targets the 5'-TACGAT-3' sequence of the 5' flank of ICB2 with high affinity and sequence specificity, eliciting an ICB2-selective inhibition/displacement of NF-Y. HxIP is readily taken up by NIH3T3 and A549 cells, and detected in the nucleus within minutes. Exposure to the polyamide at confluence resulted in a dose-dependent upregulation of topo IIα expression and enhanced formation of etoposide-induced DNA strand breaks.","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"862-75"},"PeriodicalIF":0.0,"publicationDate":"2015-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33426733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-canonical Bromodomain within DNA-PKcs Promotes DNA Damage Response and Radioresistance through Recognizing an IR-Induced Acetyl-Lysine on H2AX. DNA- pkcs中的非规范溴结构域通过识别红外诱导的H2AX上的乙酰赖氨酸促进DNA损伤反应和辐射抗性。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-06-25 DOI: 10.1016/j.chembiol.2015.05.014

Li Wang, Ling Xie, Srinivas Ramachandran, YuanYu Lee, Zhen Yan, Li Zhou, Krzysztof Krajewski, Feng Liu, Cheng Zhu, David J Chen, Brian D Strahl, Jian Jin, Nikolay V Dokholyan, Xian Chen

{"title":"Non-canonical Bromodomain within DNA-PKcs Promotes DNA Damage Response and Radioresistance through Recognizing an IR-Induced Acetyl-Lysine on H2AX.","authors":"Li Wang, Ling Xie, Srinivas Ramachandran, YuanYu Lee, Zhen Yan, Li Zhou, Krzysztof Krajewski, Feng Liu, Cheng Zhu, David J Chen, Brian D Strahl, Jian Jin, Nikolay V Dokholyan, Xian Chen","doi":"10.1016/j.chembiol.2015.05.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.05.014","url":null,"abstract":"Regulatory mechanisms underlying γH2AX induction and the associated cell fate decision during DNA damage response (DDR) remain obscure. Here, we discover a bromodomain (BRD)-like module in DNA-PKcs (DNA-PKcs-BRD) that specifically recognizes H2AX acetyl-lysine 5 (K5ac) for sequential induction of γH2AX and concurrent cell fate decision(s). First, top-down mass spectrometry of radiation-phenotypic, full-length H2AX revealed a radiation-inducible, K5ac-dependent induction of γH2AX. Combined approaches of sequence-structure modeling/docking, site-directed mutagenesis, and biochemical experiments illustrated that through docking on H2AX K5ac, this non-canonical BRD determines not only the H2AX-targeting activity of DNA-PKcs but also the over-activation of DNA-PKcs in radioresistant tumor cells, whereas a Kac antagonist, JQ1, was able to bind to DNA-PKcs-BRD, leading to re-sensitization of tumor cells to radiation. This study elucidates the mechanism underlying the H2AX-dependent regulation of DNA-PKcs in ionizing radiation-induced, differential DDR, and derives an unconventional, non-catalytic domain target in DNA-PKs for overcoming resistance during cancer radiotherapy.","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"849-61"},"PeriodicalIF":0.0,"publicationDate":"2015-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.05.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33426734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors. DNA电化学显示DNMT1甲基转移酶在结直肠癌中的高活性。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-06-25 DOI: 10.1016/j.chembiol.2015.05.019

Ariel L Furst, Jacqueline K Barton

引用次数: 21

Recent Developments in G-Quadruplex Probes. g -四重探针的最新进展。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-07-16 DOI: 10.1016/j.chembiol.2015.06.016

Dik-Lung Ma, Zhihong Zhang, Modi Wang, Lihua Lu, Hai-Jing Zhong, Chung-Hang Leung

引用次数: 147

Expanding the Toolkit for the Serine Hydrolases. 扩充丝氨酸水解酶工具箱。

Chemistry & biology Pub Date : 2015-07-23 DOI: 10.1016/j.chembiol.2015.07.002

Matthew K Ross, Ran Wang

引用次数: 3

DNMT1 and Cancer: An Electrifying Link. DNMT1和癌症:电气化的联系。

Chemistry & biology Pub Date : 2015-07-23 DOI: 10.1016/j.chembiol.2015.07.004

Nicole N Nuñez, Amelia H Manlove, Sheila S David

引用次数: 5

Internal Ribosome Entry Site-Based Bicistronic In Situ Reporter Assays for Discovery of Transcription-Targeted Lead Compounds. 基于内部核糖体进入位点的双链原位报告基因检测发现转录靶向先导化合物。

Chemistry & biology Pub Date : 2015-07-23 Epub Date: 2015-07-02 DOI: 10.1016/j.chembiol.2015.06.009

Liwei Lang, Han-Fei Ding, Xiaoguang Chen, Shi-Yong Sun, Gang Liu, Chunhong Yan

{"title":"Internal Ribosome Entry Site-Based Bicistronic In Situ Reporter Assays for Discovery of Transcription-Targeted Lead Compounds.","authors":"Liwei Lang, Han-Fei Ding, Xiaoguang Chen, Shi-Yong Sun, Gang Liu, Chunhong Yan","doi":"10.1016/j.chembiol.2015.06.009","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.009","url":null,"abstract":"Although transgene-based reporter gene assays have been used to discover small molecules targeting expression of cancer-driving genes, the success is limited due to the fact that reporter gene expression regulated by incomplete cis-acting elements and foreign epigenetic environments does not faithfully reproduce chemical responses of endogenous genes. Here, we present an internal ribosome entry site-based strategy for bicistronically co-expressing reporter genes with an endogenous gene in the native gene locus, yielding an in situ reporter assay closely mimicking endogenous gene expression without disintegrating its function. This strategy combines the CRISPR-Cas9-mediated genome-editing tool with the recombinase-mediated cassette-exchange technology, and allows for rapid development of orthogonal assays for excluding false hits generated from primary screens. We validated this strategy by developing a screening platform for identifying compounds targeting oncogenic eIF4E, and demonstrated that the novel reporter assays are powerful in searching for transcription-targeted lead compounds with high confidence.","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"957-64"},"PeriodicalIF":0.0,"publicationDate":"2015-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33879613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9