RSC Chemical Biology最新文献_第8页

Site-specific RNA modification via initiation of in vitro transcription reactions with m6A and isomorphic emissive adenosine analogs† 通过 m6A 和同构发射型腺苷类似物启动体外转录反应对特定位点 RNA 进行修饰

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-27 DOI: 10.1039/D4CB00045E

Deyuan Cong, Kfir B. Steinbuch, Ryosuke Koyama, Tyler V. Lam, Jamie Y. Lam and Yitzhak Tor

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Genome-wide mapping of G-quadruplex DNA: a step-by-step guide to select the most effective method G-quadruplex DNA 的全基因组图谱：选择最有效方法的分步指南。

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RSC Chemical Biology Pub Date : 2024-03-25 DOI: 10.1039/D4CB00023D

Silvia Galli, Gem Flint, Lucie Růžičková and Marco Di Antonio

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Introduction to ‘Medicinal Chemistry Small Molecule Probes’ 药物化学小分子探针 "简介

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RSC Chemical Biology Pub Date : 2024-03-25 DOI: 10.1039/D4CB90005G

Gemma Nixon, Khondaker Miraz Rahman and John Spencer

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Contributors to the RSC Chemical Biology Emerging Investigators Collection 2023 2023 年 RSC 化学生物学新锐研究者文集》撰稿人

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RSC Chemical Biology Pub Date : 2024-03-19 DOI: 10.1039/D4CB90013H

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Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development 伪尿嘧啶和 N1-甲基伪尿嘧啶是用于 RNA 治疗和疫苗开发的强效核苷酸类似物

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-19 DOI: 10.1039/D4CB00022F

Lyana L. Y. Ho, Gabriel H. A. Schiess, Pâmella Miranda, Gerald Weber and Kira Astakhova

{"title":"Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development","authors":"Lyana L. Y. Ho, Gabriel H. A. Schiess, Pâmella Miranda, Gerald Weber and Kira Astakhova","doi":"10.1039/D4CB00022F","DOIUrl":"10.1039/D4CB00022F","url":null,"abstract":"Modified nucleosides are integral to modern drug development, serving as crucial building blocks for creating safer, more potent, and more precisely targeted therapeutic interventions. Nucleobase modifications often confer antiviral and anti-cancer activity as monomers. When incorporated into nucleic acid oligomers, they increase stability against degradation by enzymes, enhancing the drugs’ lifespan within the body. Moreover, modification strategies can mitigate potential toxic effects and reduce immunogenicity, making drugs safer and better tolerated. Particularly, N1-methylpseudouridine modification improved the efficacy of the mRNA coding for spike protein of COVID-19. This became a crucial step for developing COVID-19 vaccine applied during the 2020 pandemic. This makes N1-methylpseudouridine, and its “parent” analogue pseudouridine, potent nucleotide analogues for future RNA therapy and vaccine development. This review focuses on the structure and properties of pseudouridine and N1-methylpseudouridine. RNA has a greater structural versatility, different conformation, and chemical reactivity than DNA. Watson–Crick pairing is not strictly followed by RNA that has more unusual base pairs and base-triplets. This requires detailed structural studies and structure–activity relationship analyses for RNA, also when modifications are incorporated. Recent successes in this direction are revised in this review. We describe recent successes with using pseudouridine and N1-methylpseudouridine in mRNA drug candidates. We also highlight remaining challenges that need to be solved to develop new mRNA vaccines and therapies.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cb/d4cb00022f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169973","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}

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Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase† 分子印迹纳米粒子揭示 Pyk2 酪氨酸激酶的调控支架特征

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-13 DOI: 10.1039/D3CB00228D

Tania M. Palhano Zanela, Milad Zangiabadi, Yan Zhao and Eric S. Underbakke

{"title":"Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase†","authors":"Tania M. Palhano Zanela, Milad Zangiabadi, Yan Zhao and Eric S. Underbakke","doi":"10.1039/D3CB00228D","DOIUrl":"10.1039/D3CB00228D","url":null,"abstract":"Pyk2 is a multi-domain non-receptor tyrosine kinase that serves dual roles as a signaling enzyme and scaffold. Pyk2 activation involves a multi-stage cascade of conformational rearrangements and protein interactions initiated by autophosphorylation of a linker site. Linker phosphorylation recruits Src kinase, and Src-mediated phosphorylation of the Pyk2 activation loop confers full activation. The regulation and accessibility of the initial Pyk2 autophosphorylation site remains unclear. We employed peptide-binding molecularly imprinted nanoparticles (MINPs) to probe the regulatory conformations controlling Pyk2 activation. MINPs differentiating local structure and phosphorylation state revealed that the Pyk2 autophosphorylation site is protected in the autoinhibited state. Activity profiling of Pyk2 variants implicated FERM and linker residues responsible for constraining the autophosphorylation site. MINPs targeting each Src docking site disrupt the higher-order kinase interactions critical for activation complex maturation. Ultimately, MINPs targeting key regulatory motifs establish a useful toolkit for probing successive activational stages in the higher-order Pyk2 signaling complex.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cb/d3cb00228d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140124598","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}

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Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30† 发现去泛素化酶 USP30 的强效选择性活性探针 (ABP)

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-13 DOI: 10.1039/D4CB00029C

Milon Mondal, Fangyuan Cao, Daniel Conole, Holger W. Auner and Edward W. Tate

{"title":"Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30†","authors":"Milon Mondal, Fangyuan Cao, Daniel Conole, Holger W. Auner and Edward W. Tate","doi":"10.1039/D4CB00029C","DOIUrl":"10.1039/D4CB00029C","url":null,"abstract":"Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme (DUB) localized at the mitochondrial outer membrane and involved in PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKβ-USP30-ACLY-regulated lipogenesis/tumorigenesis. A USP30 inhibitor, MTX652, has recently entered clinical trials as a potential treatment for mitochondrial dysfunction. Small molecule activity-based probes (ABPs) for DUBs have recently emerged as powerful tools for in-cell inhibitor screening and DUB activity analysis, and here, we report the first small molecule ABPs (IMP-2587 and IMP-2586) which can profile USP30 activity in cells. Target engagement studies demonstrate that IMP-2587 and IMP-2586 engage active USP30 at nanomolar concentration after only 10 min incubation time in intact cells, dependent on the presence of the USP30 catalytic cysteine. Interestingly, proteomics analyses revealed that DESI1 and DESI2, small ubiquitin-related modifier (SUMO) proteases, can also be engaged by these probes, further suggesting a novel approach to develop DESI ABPs.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cb/d4cb00029c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140129753","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: 0

Leveraging machine learning models for peptide–protein interaction prediction 利用机器学习模型进行多肽-蛋白质相互作用预测

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-13 DOI: 10.1039/D3CB00208J

Song Yin, Xuenan Mi and Diwakar Shukla

{"title":"Leveraging machine learning models for peptide–protein interaction prediction","authors":"Song Yin, Xuenan Mi and Diwakar Shukla","doi":"10.1039/D3CB00208J","DOIUrl":"10.1039/D3CB00208J","url":null,"abstract":"Peptides play a pivotal role in a wide range of biological activities through participating in up to 40% protein–protein interactions in cellular processes. They also demonstrate remarkable specificity and efficacy, making them promising candidates for drug development. However, predicting peptide–protein complexes by traditional computational approaches, such as docking and molecular dynamics simulations, still remains a challenge due to high computational cost, flexible nature of peptides, and limited structural information of peptide–protein complexes. In recent years, the surge of available biological data has given rise to the development of an increasing number of machine learning models for predicting peptide–protein interactions. These models offer efficient solutions to address the challenges associated with traditional computational approaches. Furthermore, they offer enhanced accuracy, robustness, and interpretability in their predictive outcomes. This review presents a comprehensive overview of machine learning and deep learning models that have emerged in recent years for the prediction of peptide–protein interactions.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cb/d3cb00208j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140124711","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: 0

Engineering cell-free systems by chemoproteomic-assisted phenotypic screening† 通过化学蛋白组辅助表型筛选技术构建无细胞系统

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-06 DOI: 10.1039/D4CB00004H

Zarina Levitskaya, Zheng Ser, Hiromi Koh, Wang Shi Mei, Sharon Chee, Radoslaw Mikolaj Sobota and John F. Ghadessy

{"title":"Engineering cell-free systems by chemoproteomic-assisted phenotypic screening†","authors":"Zarina Levitskaya, Zheng Ser, Hiromi Koh, Wang Shi Mei, Sharon Chee, Radoslaw Mikolaj Sobota and John F. Ghadessy","doi":"10.1039/D4CB00004H","DOIUrl":"10.1039/D4CB00004H","url":null,"abstract":"Phenotypic screening is a valuable tool to both understand and engineer complex biological systems. We demonstrate the functionality of this approach in the development of cell-free protein synthesis (CFPS) technology. Phenotypic screening identified numerous compounds that enhanced protein production in yeast lysate CFPS reactions. Notably, many of these were competitive ATP kinase inhibitors, with the exploitation of their inherent substrate promiscuity redirecting ATP flux towards heterologous protein expression. Chemoproteomic-guided strain engineering partially phenocopied drug effects, with a 30% increase in protein yield observed upon deletion of the ATP-consuming SSA1 component of the HSP70 chaperone. Moreover, drug-mediated metabolic rewiring coupled with template optimization generated the highest protein yields in yeast CFPS to date using a hitherto less efficient, but more cost-effective glucose energy regeneration system. Our approach highlights the utility of target-agnostic phenotypic screening and target identification to deconvolute cell-lysate complexity, adding to the expanding repertoire of strategies for improving CFPS.","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/cb/d4cb00004h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046603","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: 0

Introduction to ‘The Epitranscriptome’ 表转录组 "简介

IF 4.1

RSC Chemical Biology Pub Date : 2024-03-06 DOI: 10.1039/D4CB90006E

Ralph E. Kleiner, Claudia Höbartner and Guifang Jia

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