Stereoretentive post-translational protein editing

Journal article

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-proteinl-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.

Authors: Fu, X-P; Yuan, Y; Jha, A; Levin, N; Giltrap, AM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: ACS Central Science
• Volume: 9
• Issue: 3
• Pages: 405-416
• Publication date: 2023-02-24
• Acceptance date: 2023-02-24
• DOI: 10.1021/acscentsci.2c00991
• EISSN: 2374-7951
• ISSN: 2374-7943
• Pmid: 36968537
• Language: English
• Keywords: FFR; chemical sciences