Assembling branched and macrocyclic peptides on proteins

Abstract

A two-step, biocompatible strategy enables site-specific generation of branched and macrocyclic peptide–protein conjugates. Solvent-exposed cysteines on proteins are modified by a small bifunctional reagent at near-physiological pH, followed by cyanopyridine–aminothiol click reactions to create branched or macrocyclic peptide architectures. This method offers design strategies for next-generation protein therapeutics.