New perspectives in peptide Chemistry by multiple N-methylation

To achieve oral bioavailability of peptides, we envisioned multiple N-methylation. Here we highlight the efficient methods for the synthesis of N-methylated ammo acids in solution and on solid support. The utility of multiple N-methylation in achieving better pharmacokinetic profile of peptides, including enzymatic stability and oral bioavailability, is presented. We also show that multiple N-methylation results in enhanced receptor subtype selectivity within the integrin family.