dna编码文库的最新进展：从共价靶向到蛋白质谱分析。

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology Pub Date : 2025-09-30 DOI:10.1016/j.sbi.2025.103163

Rui Jin , Xiaojie Lu

{"title":"dna编码文库的最新进展：从共价靶向到蛋白质谱分析。","authors":"Rui Jin , Xiaojie Lu","doi":"10.1016/j.sbi.2025.103163","DOIUrl":null,"url":null,"abstract":"<div><div>DNA-encoded library (DEL) technology has enabled efficient discovery of both non-covalent and covalent inhibitors, with covalent binders typically identified via covalent DELs (CoDELs) containing diverse electrophilic warheads. Recent developments have expanded CoDEL applications beyond cysteine to residues like lysine, tyrosine, arginine, and glutamic acid. The integration of CoDEL with activity-based protein profiling (ABPP) has further enabled the identification of potential protein targets for CoDEL screening using residue-selective warheads. Additionally, proteome profiling with fully-functionalized tags has guided target identification for focused DELs with privileged structures. This review highlights recent advances in CoDEL technologies for targeting both cysteine and non-cysteine residues, and discusses how proteomics facilitates hit discovery through CoDELs and focused DELs.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"95 ","pages":"Article 103163"},"PeriodicalIF":6.1000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recent advances in DNA-encoded libraries: From covalent targeting to protein profiling\",\"authors\":\"Rui Jin , Xiaojie Lu\",\"doi\":\"10.1016/j.sbi.2025.103163\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>DNA-encoded library (DEL) technology has enabled efficient discovery of both non-covalent and covalent inhibitors, with covalent binders typically identified via covalent DELs (CoDELs) containing diverse electrophilic warheads. Recent developments have expanded CoDEL applications beyond cysteine to residues like lysine, tyrosine, arginine, and glutamic acid. The integration of CoDEL with activity-based protein profiling (ABPP) has further enabled the identification of potential protein targets for CoDEL screening using residue-selective warheads. Additionally, proteome profiling with fully-functionalized tags has guided target identification for focused DELs with privileged structures. This review highlights recent advances in CoDEL technologies for targeting both cysteine and non-cysteine residues, and discusses how proteomics facilitates hit discovery through CoDELs and focused DELs.</div></div>\",\"PeriodicalId\":10887,\"journal\":{\"name\":\"Current opinion in structural biology\",\"volume\":\"95 \",\"pages\":\"Article 103163\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current opinion in structural biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0959440X25001812\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in structural biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959440X25001812","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

dna编码文库（DEL）技术能够有效地发现非共价和共价抑制剂，通常通过含有多种亲电弹头的共价文库（CoDELs）识别共价结合物。最近的发展已经将CoDEL的应用范围从半胱氨酸扩展到赖氨酸、酪氨酸、精氨酸和谷氨酸等残基。CoDEL与基于活性的蛋白质谱分析（ABPP）的整合进一步使使用残基选择性弹头识别CoDEL筛选的潜在蛋白质靶标成为可能。此外，具有全功能化标签的蛋白质组分析指导了具有特权结构的集中DELs的目标识别。本文综述了针对半胱氨酸和非半胱氨酸残基的CoDEL技术的最新进展，并讨论了蛋白质组学如何通过CoDEL和聚焦del促进hit发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Recent advances in DNA-encoded libraries: From covalent targeting to protein profiling

DNA-encoded library (DEL) technology has enabled efficient discovery of both non-covalent and covalent inhibitors, with covalent binders typically identified via covalent DELs (CoDELs) containing diverse electrophilic warheads. Recent developments have expanded CoDEL applications beyond cysteine to residues like lysine, tyrosine, arginine, and glutamic acid. The integration of CoDEL with activity-based protein profiling (ABPP) has further enabled the identification of potential protein targets for CoDEL screening using residue-selective warheads. Additionally, proteome profiling with fully-functionalized tags has guided target identification for focused DELs with privileged structures. This review highlights recent advances in CoDEL technologies for targeting both cysteine and non-cysteine residues, and discusses how proteomics facilitates hit discovery through CoDELs and focused DELs.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Current opinion in structural biology 生物-生化与分子生物学

CiteScore

12.20

自引率

2.90%

发文量

179

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation