%0 Journal Article
%T A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins
%J -
%D 2018
%R https://doi.org/10.1038/s41557-018-0154-0
%X Conjugates between proteins and small molecules enable access to a vast chemical space that is not achievable with either type of molecule alone; however, the paucity of specific reactions capable of functionalizing proteins and natural products presents a formidable challenge for preparing conjugates. Here we report a strategy for conjugating electron-rich (hetero)arenes to polypeptides and proteins. Our bioconjugation technique exploits the electrophilic reactivity of an oxidized selenocysteine residue in polypeptides and proteins, and the electron-rich character of certain small molecules to provide bioconjugates in excellent yields under mild conditions. This conjugation chemistry enabled the synthesis of peptide¨Cvancomycin conjugates without the prefunctionalization of vancomycin. These conjugates have an enhanced in vitro potency for resistant Gram-positive and Gram-negative pathogens. Additionally, we show that a 6£¿kDa affibody protein and a 150£¿kDa immunoglobulin-G antibody could be modified without diminishing bioactivity
%U https://www.nature.com/articles/s41557-018-0154-0