Intrinsically Photoswitchable α/β Peptides toward Two-State Foldamers

Abstract

A simple, unsaturated, E-Z photoisomerizable β-amino acid, (Z)-3-aminoprop-2-enoic acid, has been introduced into peptide foldamers through a one-pot chemical coupling, based on Pd/Cu-catalyzed olefin oxidative amidation, between two peptide segments carrying, respectively, a -Gly-NH₂ residue at the C-terminus and an acryloyl group at the N-terminus. Reversible conversion between the Z and E configurations of the 3-aminoprop-2-enoic linkage was achieved photochemically. A crystallographic analysis on two model compounds shed light on the consequences, in terms of 3D structure and self-association properties, brought about by the different configuration of the unsaturated linkage. As a proof of concept, E-Z photoisomerization of a 3-aminoprop-2-enoic acid residue, inserted as the junction between two conformationally distinct peptide domains (one helical while the other β-sheet promoter), allowed supramolecular self-association to be reversibly turned on/off.

Keywords: chemical ligation; foldamers; peptidomimetics; photoisomerization; supramolecular chemistry.