Theoretical study of β2,3-peptide models

Conformational features of alpha,beta-disubstituted beta(2,3)-dipeptide models have been studied with quantum mechanics method. Geometries were optimized with the HF/6-31G** method, and energies were evaluated with the B3LYP/6-31G** method. Solvent effect was evaluated with the SCIPCM method. For (2S,3S)-beta(2,3)-dipeptide model 1, a six-membered-ring hydrogen bonded structure is most stable. However, the conformation corresponding to the formation of the 14-helix is only about 1.7 kcal/mol less stable in methanol solution, indicating that the 14-helix is favored if a (2S,3S)-beta(2,3)-polypeptide contains more than 5 residues. On the other hand, the conformation corresponding to the formation of beta-sheet is most stable for (2R,3S)-beta(2,3)-dipeptide model 2, suggesting that this type of beta-peptides is intrinsically favored for the formation of P-sheet secondary structure.