{"title":"Optimizing Solid-Phase Protein Synthesis Using CPG-2000 and a Nickel-Cleavable SNAC-tag Linker","authors":"Jianyi Han, Bobo Dang","doi":"10.1021/acs.orglett.5c00109","DOIUrl":null,"url":null,"abstract":"Solid-phase chemical ligation (SPCL) is a powerful method for simplifying protein synthesis but faces challenges with orthogonal protection strategies, suboptimal solid supports, and limited cleavable linkers. In this study, we optimized SPCL by combining low-loading controlled-pore glass (CPG-2000) with a nickel-cleavable SNAC-tag linker. This system enabled the successful assembly of five peptide fragments and the efficient synthesis of a 131-amino-acid de novo protein, achieving a 25% yield.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"27 1","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.orglett.5c00109","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Solid-phase chemical ligation (SPCL) is a powerful method for simplifying protein synthesis but faces challenges with orthogonal protection strategies, suboptimal solid supports, and limited cleavable linkers. In this study, we optimized SPCL by combining low-loading controlled-pore glass (CPG-2000) with a nickel-cleavable SNAC-tag linker. This system enabled the successful assembly of five peptide fragments and the efficient synthesis of a 131-amino-acid de novo protein, achieving a 25% yield.
期刊介绍:
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.