Nucleation effects in peptide foldamers

Oligomers composed of β ³-amino acid residues and a mixture of α- and β ³-residues have emerged as proteolytically stable structural mimics of α-helices. An attractive feature of these oligomers is that they adopt defined conformations in short sequences. In this manuscript, we evaluate the impact of β ³-residues as compared to their α-amino acid analogs in prenucleated helices. Our hydrogen-deuterium exchange results suggest that heterogeneous sequences composed of "αααβ" repeats are conformationally more rigid than the corresponding homogeneous α-peptide helices, with the macrocycle templating the helical conformation having a significant influence.