Multifunctional Cys labeling-directed N-terminus-selective stapling strategy development

Protein bioconjugation technology integrates the fields of synthetic chemistry and molecular biology, where N-terminal amino groups are increasingly targeted for site-specific modification strategies due to their unique properties. Herein, we report a novel approach to achieve bioconjugation of cysteine and N-terminal amino groups using multifunctional allyl sulfone-activated esters. The experiments were performed in a biocompatible environment (pH 7.4, 10 mM PBS, 37 °C) with universal sequence compatibility for unprotected random peptides of different lengths. Cyclic peptides show desirable late functionalization modifications (including biotin, alkynyl, and PEG et al.).