Delta-peptides and delta-amino acids as tools for peptide structure design--a theoretical study

An overview on all possible helix types in oligomers of delta-amino acids (delta-peptides) and their stabilities is given on the basis of a systematic conformational analysis employing various methods of ab initio MO theory (HF/6-31G*, B3LYP/6-31G*, PCM//HF/6-31G*). A wide variety of novel helical structures with hydrogen-bonded pseudocycles of different size are predicted. Since a delta-amino acid constituent may replace a dipeptide unit in alpha-peptides, there are close relationships between the secondary structures of peptides with delta-amino acid residues and typical secondary structures of alpha-peptides. However, the preference of gauche conformations at the central C(beta)-C(gamma) bonds of delta-amino acids, which correspond to the peptide linkages in alpha-peptides, over staggered ones makes completely novel structure alternatives for helices and turns more probable. The peculiarities of beta-turn formation by sugar amino acids derived from delta-amino acids are compared with the turn formation in delta-amino acid residues and in alpha-peptides. The considerable potential of secondary structure formation in delta-peptides and single delta-amino acid constituents predicted by ab initio MO theory may stimulate experimental work in the field of peptide and foldamer design.