Theoretical Studies of β-Peptide Models

The key conformations of β -dipeptide models 4 − 9 have been studied with quantum mechanics calculations including a self-consistent isodensity solvation model to evaluate the tendency of β -sheet, 14-helix, and 12-helix formation of β -peptide models. The most stable conformation of dipeptide models 5 − 7 is a formal six-membered-ring (C6) hydrogen-bonded structure, although the hydrogen bond is very weak because of a bad N−H- - -O angle. Many local conformational minima with folded structures are found. This is attributed to internal non-hydrogen-bonded electrostatic (or dipole) interactions. Most interestingly, for dipeptide model 7, the most stable conformation in polar solvent is predicted to correspond to the 14-helix. The conformations for β -sheet, 14-helix, and 12-helix are much destabilized by electrostatic interactions in the gas phase but significantly benefit from the polar solvent effect. The 12-helix is intrinsically less favorable than the 14-helix. The key difference between 14- and 12-helices is the dihedral angle ( μ ) about the C α −C β bond the former is about 60° while the latter is about 90°. Comparatively, β 3 -peptides have greater 14-helical propensity than β 2 -peptides. The five-membered and six-membered rings in dipeptide models 8 and 9 promote the 12-helix and 14-helix conformations, respectively. Calculations for β -hexapeptide models 10 and 11 indicate somewhat stronger hydrogen bonding in the 12-helix than in the 14-helix structure.