Chemical Synthesis of Peptides and Proteins Bearing Base‐Labile Post‐Translational Modifications: Evolution of the Methods in Four Decades

Abstract

AbstractThe S‐palmitoylation on Cys residue and O‐acetylation on Ser/Thr residues are two types of base‐labile post‐translational modifications (PTMs) in cells. The lability of these PTMs to bases and nucleophiles makes the peptides/proteins bearing S‐palmitoyl or O‐acetyl groups challenging synthetic targets, which cannot be prepared via the standard Fmoc‐SPPS and native chemical ligation. In this review, we summarized the efforts towards their preparation in the past 40 years, with the focus on the evolution of synthetic methods.