The proximity-enabled sulfur fluoride exchange reaction in the protein context.

ABSTRACT: The proximity-enabled sulfur(vi) fluoride exchange (SuFEx) reaction generates specific covalent linkages between proteins in cells and in vivo, which opens innovative avenues for studying elusive protein-protein interactions and developing potent covalent protein drugs. To exploit the power and expand the applications of covalent proteins, covalent linkage formation between proteins is the critical step, for which fundamental kinetic and essential properties remain unexplored. Herein, we systematically studied SuFEx kinetics in different proteins and conditions. In contrast to in small molecules, SuFEx in interacting proteins conformed with a two-step mechanism involving noncovalent binding, followed by covalent bond formation, exhibiting nonlinear rate dependence on protein concent

SUBMITTER: Yu B 

PROVIDER: S-EPMC10370592 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature