Xiaoyi Li, Nimit L. Patel, Joseph Kalen, Martin J. Schnermann
{"title":"Benzyl Ammonium Carbamates Undergo Two-Step Linker Cleavage and Improve the Properties of Antibody Conjugates","authors":"Xiaoyi Li, Nimit L. Patel, Joseph Kalen, Martin J. Schnermann","doi":"10.1002/anie.202417651","DOIUrl":null,"url":null,"abstract":"Towards the goal of identifying an intrinsically polar linker domain, we report that benzyl α-ammonium carbamates (BAC) undergo a tandem 1,6–1,2 elimination sequence to release secondary amines. A zwitterionic BAC linker variant is found to improve the labeling and reduce antibody aggregation when compared to a conventional and a cationic BAC linker. Finally, fluorescence imaging studies demonstrate that the model payload is released in antigen-expressing cells and tumors with high specificity.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"1 1","pages":""},"PeriodicalIF":16.1000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie International Edition","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/anie.202417651","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Towards the goal of identifying an intrinsically polar linker domain, we report that benzyl α-ammonium carbamates (BAC) undergo a tandem 1,6–1,2 elimination sequence to release secondary amines. A zwitterionic BAC linker variant is found to improve the labeling and reduce antibody aggregation when compared to a conventional and a cationic BAC linker. Finally, fluorescence imaging studies demonstrate that the model payload is released in antigen-expressing cells and tumors with high specificity.
期刊介绍：
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
