Fast and Stable N-Terminal Cysteine Modification through Thiazolidino Boronate Mediated Acyl Transfer.

ABSTRACT: We report a novel conjugation of N-terminal cysteines (NCys) that proceeds with fast kinetics and exquisite selectivity, thereby enabling facile modification of NCys-bearing proteins in complex biological milieu. This new NCys conjugation proceeds via a thiazolidine boronate (TzB) intermediate that results from fast (k₂ : ≈5000 m^-1  s^-1 ) and reversible conjugation of NCys with 2-formylphenylboronic acid (FPBA). We designed a FPBA derivative that upon TzB formation elicits intramolecular acyl transfer to give N-acyl thiazolidines. In contrast to the quick hydrolysis of TzB, the N-acylated thiazolidines exhibit robust stability under physiologic conditions. The utility of the TzB-mediated NCys conjugation is demonstrated by rapid and non-disruptive labeling

SUBMITTER: Li K 

PROVIDER: S-EPMC8041485 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature