Synthesis of N-methylated peptides: on-resin methylation and microwave-assisted couplings.
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.
Department of Chemistry, Faculty of Sciences, University of Copenhagen, Frederiksberg, Denmark.
Renée
R
Roodbeen
Knud J
KJ
Jensen
D000596:Amino Acids / Q000737:chemistry; D008745:Methylation; D008872:Microwaves; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods
D000596:Amino Acids; D010455:Peptides; D012117:Resins, Synthetic