Stereoretentive Post-Translational Protein Editing

作者：Xia‐Ping Fu, Yizhi Yuan, Ajay Jha, Nikita Levin, Andrew M. Giltrap, Jack Ren, Dimitrios Mamalis, Shabaz Mohammed, Benjamin G. Davis · 发表于：ACS Central Science · 年份：2023 · DOI：10.1021/acscentsci.2c00991 · 被引用次数：37 · 研究领域：RNA and protein synthesis mechanisms、Click Chemistry and Applications、Chemical Synthesis and Analysis

High Resolution Image Download MS PowerPoint Slide Chemical post-translational methods allow convergent side-chain editing of proteins without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side chains via C–C bond formation, using off-protein carbon-centered C· radicals added to unnatural amino acid radical acceptor (SOMOphile, singly occupied molecular orbital (SOMO)) “tags” such as dehydroalanine, are benign and wide-ranging. However, they also typically create epimeric mixtures of d /l -residues. Here, we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-protein l -alanyl C β · radicals, allows C β –H γ, C β –O γ, C β –Se γ, C β –B γ, and C β –C γ bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid precursor. This methodology shows great potential to explore protein side-chain diversity and function and in the construction of useful bioconjugates.