Membrane channel forming polypeptides. 270-MHz proton magnetic resonance studies of the aggregation of the 11-21 fragment of suzukacillin in organic solvents

Abstract

270-MHz ¹H NMR studies of the 11-21 suzukacillin fragment Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Val-Aib-Aib-OMe (11-G) and its analogue Boc-Ala-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-A) have been carried out in CDCl₃ and (CD₃)₂SO. The NH chemical shifts and their temperature coefficients have been measured as a function of peptide concentration in both solvents. It is established that replacement of Gln by Ala is without effect on backbone conformation. Both peptides adopt highly folded 3₁₀ helical conformations stabilized by seven intramolecular 4 → 1 hydrogen bonds. Nonlinear temperature dependences are demonstrated for free NH groups in the Gln(1) peptide. Aggregation is mediated by intermolecular hydrogen bonds formed by solvent-exposed NH groups. A major role for the Gln side chain in peptide association is suggested by differences in the NMR behavior of the Gln(1) and Ala(1) peptides. For the Gln(1) peptide in CDCl₃, the carboxamide side chain carbonyl group forms an intramolecular hydrogen bond to the peptide backbone, while the trans side chain NH shows evidence for intermolecular interactions. In (CD₃)₂SO, the cis carboxamide NH is involved in intermolecular hydrogen bonding. The possible role of the central Gln residue in sta-bilizing aggregates of peptide channel formers is discussed, and a model for hexameric association is postulated.