{"title":"DNA-Encoded Library Technology─A Catalyst for Covalent Ligand Discovery","authors":"Paige Dickson*, ","doi":"10.1021/acschembio.3c00803","DOIUrl":null,"url":null,"abstract":"<p >The identification of novel covalent ligands for therapeutic purposes has long depended on serendipity, with dedicated hit finding techniques emerging only in the early 2000s. Advances in chemoproteomics have enabled robust characterization of putative drugs to derisk the unique liabilities associated with covalent hit molecules, leading to a renewed interest in this targeting modality. DNA-encoded library (DEL) technology has similarly emerged over the past two decades as a highly efficient method to identify new chemical equity toward protein targets of interest. A number of commercial and academic groups have reported methods in covalent DEL synthesis and hit identification; however, it is evident that there is still much to be done to fully realize the power of this technology for covalent ligand discovery. This perspective will explore the current approaches in covalent DEL technology and reflect on the next steps to advance this field.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Biology","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschembio.3c00803","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The identification of novel covalent ligands for therapeutic purposes has long depended on serendipity, with dedicated hit finding techniques emerging only in the early 2000s. Advances in chemoproteomics have enabled robust characterization of putative drugs to derisk the unique liabilities associated with covalent hit molecules, leading to a renewed interest in this targeting modality. DNA-encoded library (DEL) technology has similarly emerged over the past two decades as a highly efficient method to identify new chemical equity toward protein targets of interest. A number of commercial and academic groups have reported methods in covalent DEL synthesis and hit identification; however, it is evident that there is still much to be done to fully realize the power of this technology for covalent ligand discovery. This perspective will explore the current approaches in covalent DEL technology and reflect on the next steps to advance this field.
长期以来,用于治疗目的的新型共价配体的鉴定一直依赖于偶然性,而专门的命中发现技术直到本世纪初才出现。化学蛋白质组学的进步使人们能够对可能的药物进行强有力的特征描述,从而发现与共价配体分子相关的独特缺陷,从而重新激发了人们对这种靶向方式的兴趣。DNA 编码文库(DEL)技术在过去二十年中同样崭露头角,成为一种高效的方法,用于鉴定针对感兴趣的蛋白质靶点的新化学权益。一些商业和学术团体已经报道了共价 DEL 合成和命中识别方法;然而,要充分发挥这项技术在共价配体发现方面的威力,显然还有许多工作要做。本视角将探讨共价 DEL 技术的现有方法,并思考推动这一领域发展的下一步措施。
期刊介绍:
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.