Automated Synthesis of Hydrocarbon-Stapled Peptides Via Microwave Assisted Ring-Closing Metathesis

Introduction

Peptide stapling is an effective strategy for stabilizing α-helices, which are important structural motifs that dictate the biological activity of various peptides and proteins. Hydrocarbon stapling in particular has emerged as a powerful method for stabilizing α-helices and has produced several examples of peptides with higher target affinity and with dramatically increased protease resistance. Additionally, some hydrocarbon-stapled peptides have been shown to have greater cell permeability and in vivo activity than their unstapled analogues, which has further invigorated efforts to use α-helical peptides for therapeutic applications.