The role of primary sequence in helical control compared across short α- and β(3)-peptides

α-helices are the most common form of secondary structure found in proteins. In order to study controlled protein folding, as well as manipulate the interface of helical peptides with targets in protein-protein interactions, many techniques have been developed to induce and stabilize α-helical structure in short synthetic peptides. Furthermore, short, non-natural β-peptides have been established that fold into predictable 14-helices that mimic α-helical structure. We created a panel of short 6-8 residue α- and β-peptides that used confirmed primary sequence design features which influence helical control and directly compared the helicity across peptides with the most minimal epitopes. Using CD spectroscopy, we found that both α- and β-peptides abided by their respective design principles, with no significant "cross-helicity" inducing an α- or a β-peptide to fold into the oppositely controlled helix. Generally, the β-peptide of the most optimal sequence displayed the largest percent of 14-helicity, whereas the two α-peptides of most favorable design showed some α-helicity and a marked 310-helical contribution. Overall, the results can inform future peptidomimetic designs, especially in the development of short, structured peptides with biological function.