Incorporation of pseudoproline monomer (Fmoc-Thr[ψMe,Mepro]–OH) facilitates efficient solid-phase synthesis of difficult peptides

Abstract

Solid-Phase Peptide Synthesis (SPPS) is a convenient and efficient method by which to prepare peptides. However, the sequences of compounds classified as “difficult” show aggregation of growing peptide chains and their synthesis is extremely challenging by stepwise SPPS. In this context, the concourse of pseudoproline derivatives helps to break the aggregation and facilitates the synthesis. Although pseudoproline moieties are traditionally incorporated as dipeptides, the possibility of using only the monomer adds flexibility to the synthesis. Herein, the introduction of the most hindered β-branched Thr[ψMe,Mepro] derivative is studied in terms of how difficult is its acylation is by the following amino acid and the impact of its use on the final purity of two well-known ”difficult peptides”.