Infrared studies on the conformation of synthetic alamethicin fragments and model peptides containing α-aminoisobutyric acid

Abstract

Infrared studies of synthetic alamethicin fragments and model peptides containing α-aminoisobutyric acid (Aib) have been carried out in solution. Tripeptides and larger fragments exhibit a strong tendency to form β turns, stabilized by 4 -> 1 10-atom hydrogen bonds. Dipeptides show less well-defined structures, though C₅ and C₇ conformations are detectable. Conformational restrictions imposed by Aib residues result in these peptides populating a limited range of states. Integrated intensities of the hydrogen-bonded N-H stretching band can be used to quantitate the number of intramolecular hydrogen bonds. Predictions made from infrared data are in excellent agreement with nuclear magnetic resonance and X-ray diffraction studies. Assignments of the urethane and tertiary amide carbonyl groups in the free state have been made in model peptides. Shifts to lower frequency on hydrogen bonding are observed for the carbonyl groups. The 1-6 segment of alamethicin is shown to adopt a 3₁₀ helical structure stabilized by four intramolecular hydrogen bonds. The fragments Boc-Leu-Aib-Pro-Val-Aib-OMe (12-16) and Boc-Gly-Leu-Aig-Pro-Val-Aib-OMe (11-16) possess structures involving 4 → 1 and 5 → 1 hydrogen bonds. Supporting evidence for these structures is obtained from proton nuclear magnetic resonance studies.