Rapid On‐Resin N‐Formylation of Peptides as One‐Pot Reaction

Abstract

AbstractN‐formylation is a common pre‐ and post‐translational modification of the N‐terminus or the lysine side chain of peptides and proteins that plays a role in the initiation of immune responses, gene expression, or epigenetics. Despite its high biological relevance, protocols for the chemical N‐formylation of synthetic peptides are scarce. The few available methods are elaborate in their execution and the yields are highly sequence‐dependent. We present a rapid, easy‐to‐use one‐pot procedure that runs at room temperature and can be used to formylate protected peptides at both the N‐terminus and the lysine side chain on the resin in near‐quantitative yields. Only insensitive, storage‐stable standard chemicals – formic acid, acetic anhydride, pyridine and DMF – are used. Formylation works for both short and long peptides of up to 34 amino acids and over the spectrum of canonical amino acids.