Conformational variability in short acyclic peptides. Stabilization of multiple β-turn structures in organic solvents
The conformational characteristics of three hexapeptides Boc-Leu-Xxx-Val-Leu-Aib-Val-OMe(Xxx = Ala 1, D-Ala2, Gly 3; Aib =α-aminoisobutyryl) have been probed in CDCl3 solution by NMR methods using solvent perturbation of chemical shifts and radical broadening of NH resonances to delineate intramolecularly hydrogen bonded NH groups. Nuclear Overhauser effects (NOEs) provide additional information on preferred backbone conformations. The substituent at position 2 acts as a major conformational determinant. While a continuous 310 helical conformation is favoured for the peptide with Xxx = Ala, a multiple β-turns conformation is supported by both NMR and CD data for the peptide with Xxx =D-Ala. In the peptide with Xxx = Gly CD and NMR data suggest that both 310 helical and multiple turns conformations are simultaneously populated. The results suggest that incorporation of D-amino acids and Aib residues into all L-sequences may prove useful in generating sequences containing multiple turns.