Diaminodiacid-based solid-phase synthesis of all-hydrocarbon stapled α-helical peptides?

Organic & Biomolecular Chemistry Pub Date: 2015-04-29 DOI: 10.1039/C5OB00741K

Abstract

An alternative stapling strategy is described herein using Fmoc-solid phase peptide synthesis (SPPS) that employed pre-prepared diaminodiacid building blocks to introduce all-hydrocarbon staples into peptides by on-resin cyclization. Compared to unstapled native peptides, diaminodiacid-based stapled peptides exhibited an increased α-helicity ratio and stability toward protease. Moreover, the linkage length was found to affect the bioactivity of the peptides and their ability to inhibit the Wnt pathway. Therefore, the new stapling method provides an alternative way to obtain stapled peptides with tunable linkers of diaminodiacids.

Graphical abstract: Diaminodiacid-based solid-phase synthesis of all-hydrocarbon stapled α-helical peptides
Recommended Literature