Differential Impact of β and γ Residue Preorganization on α/β/γ-Peptide Helix Stability in Water

Cyclic constraints have proven to be very effective for preorganizing beta-amino acid residues and thereby stabilizing beta- and alpha/beta-peptide helices, but little is known about possible preorganization effects among gamma residues. Here we assess and compare the impact of cyclic preorganization of beta and gamma residues in the context of a specific alpha/beta/gamma-peptide helix. The results show that beta residue preorganization is critical for helix stability but that residue preorganization is less important.