Synthesis of N-methylated peptides: On-resin methylation and microwave-assisted couplings

Abstract

N-Methylation may positively influence the pharmacokinetic properties of peptides by improving oral availability and in vivo half-life. Additionally, target affinity and specificity may be improved. Here, we describe the solid-phase N-methylation of peptides using direct alkylation. This method allows a rapid N-methyl scan of synthetic, bioactive peptides. Additionally, a microwave-enhanced method for the difficult coupling onto the methylated N terminus is provided. © Springer Science+Business Media, New York 2013.