Synthesis and stabilities of peptide-based [1]rotaxanes: molecular grafting onto lasso peptide scaffolds

Abstract

The chemical synthesis of peptide-based [1]rotaxanes (lasso peptides) was achieved by [2]rotaxane formation followed by two chemoselective ligation reactions. Our approach enabled incorporation of various peptide sequences into a common rotaxane structure. The synthetic lasso peptides were characterized by NMR, chromatography, and partial degradation by proteases. A linear peptide epitope grafted onto the rotaxane scaffold showed significantly improved proteolytic stability.