期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 32, 页码 12657-12662出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b04744
关键词
-
资金
- Novartis Institutes for BioMedical Research
- Novartis-Berkeley Center for Proteomics and Chemistry Technologies (NB-CPACT)
- NSF-GRFP [DGE 1106400]
- NIH [ES004705, GM121383, S10OD023532]
We report a data-driven, physical organic approach to the development of new methionine-selective bioconjugation reagents with tunable adduct stabilities. Statistical modeling of structural features described by intrinsic physical organic parameters was applied to the development of a predictive model and to gain insight into features driving the stability of adducts formed from the chemoselective coupling of oxaziridine and methionine thioether partners through Redox Activated Chemical Tagging (ReACT). From these analyses, a correlation between sulfimide stabilities and sulfimide nu (C=O) stretching frequencies was revealed. We exploited the rational gains in adduct stability exposed by this analysis to achieve the design and synthesis of a bis-oxaziridine reagent for peptide stapling. Indeed, we observed that a macrocyclic peptide formed by ReACT stapling at methionine exhibited improved uptake into live cells compared to an unstapled congener, highlighting the potential utility of this unique chemical tool for thioether modification. This work provides a template for the broader use of data-driven approaches to bioconjugation chemistry and other chemical biology applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据