The potential of N-alkoxymethyl groups as peptide backbone protectants

Abstract

In this study, the potential of N-alkoxymethyl groups as protectants for the peptide backbone has been investigated. These groups were found to be compatible with the standard conditions of Fmoc/tBu SPPS, and can be cleaved off from the peptide backbone by acids. Thus, backbone N-alkoxymethyl groups may be useful to prevent undesired side-reactions and/or interchain aggregation during peptide elongation on the solid-phase. However, the main issue for their application as protecting groups is the difficulty to incorporate them into the peptide backbone.