A convenient microwave-enhanced solid-phase synthesis of short chain N-methyl-rich peptides.

Structural modification of the peptide backbone via N-methylation is a powerful tool to modulate the pharmacokinetic profile and biological activity of peptides. Here we describe a rapid and highly efficient microwave(MW)-assisted Fmoc/tBu solid-phase method to prepare short chain N-methyl-rich peptides, using Rink amide p-methylbenzhydrylamine (MBHA) resin as solid-phase support. This method produces peptides in high yield and purity, and reduces the time required for Fmoc-N-methyl amino acid coupling.