Peptide design: influence of a guest Aib-Pro segment on the stereochemistry of an Oligo-Val sequence - solution conformations and crystal structure of Boc-(Val)₂-Aib-Pro-(Val)₃-OMe

Abstract

The peptide Boc-Val-Val-Aib-Pro-Val-Val-Val-OMe has been synthesized to investigate the effect of introduction of a strong β-turn promoting guest segment into an oligopeptide with a tendency to form extended structures. ¹H-nmr studies in solution using analysis of NH group solvent accessibility and nuclear Overhauser effects suggest an appreciable solvent dependence of conformations. In chloroform a 3₁₀-helical structure is favored while in dimethylsulfoxide an Aib-Pro -turn with extended arms on either side is suggested. In the crystal, the backbone forms a somewhat distorted 3₁₀-helix despite the presence of a Pro residue in the middle. Among the four possible intrahelical hydrogen bonds three are of the 4 →1 type and one 5→ 1. Head-to-tail NH...O=C hydrogen bonds link the helical molecules into continuous columns. The space group is P2₁2₁2₁ with a = 11.320(2), b = 19.889(3), and c = 21.247(3) Å.