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

Research paper by Renée R Roodbeen, Knud J KJ Jensen

Indexed on: 15 Aug '13Published on: 15 Aug '13Published in: Methods in molecular biology (Clifton, N.J.)


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.