Polyfluorinated reagents for peptide stapling

Abstract

Peptide stapling has emerged as a valuable approach for modulating peptide structures and enhancing their functional properties, with broad applications for drug discovery and biomolecular engineering. Among the diverse stapling strategies, polyfluorinated reagent-mediated approaches stand out due to their unique ability to provide desirable physicochemical properties such as improved stability, lipophilicity, and binding affinity. This review highlights recent advancements in polyfluorinated reagents for native peptide stapling, focusing on three major classes: arylation, vinylation, and amidation reagents. These reagents enable precise peptide modifications by leveraging the reactivity and selectivity modulated by fluorine substituents, facilitating the engineering of native peptides and biologics.