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

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