Stereoretentive Post-Translational Protein Editing.
ACS Cent Sci
; 9(3): 405-416, 2023 Mar 22.
Article
em En
| MEDLINE
| ID: mdl-36968537
ABSTRACT
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 Cß· radicals, allows Cß-Hγ, Cß-Oγ, Cß-Seγ, Cß-Bγ, and Cß-Cγ 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Cent Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Reino Unido