Mixed micelle formation between gramicidin-S and a nonionic detergent: a nuclear magnetic resonance model study of peptide/detergent aggregation

The interaction of the cyclic decapeptide antibiotic gramicidin-S (GrS) with the nonionic detergent octaethylene glycol mono-n-dodecyl ether was studied by NMR spectroscopy. Detergent binding led to a slightly altered average conformation in the d-Phe side chains of the peptide. The changing diamagnetic shielding of nearby protons resulted in chemical shift variations, the largest effect being observed for the d-Phe C _α proton. The continuous upfield shift of this proton resonance, indicating rapid exchange of the peptide between detergent-associated and unassociated states, was employed for an evaluation of the detergent/peptide aggregation equilibria. The nonlinear binding plot thus obtained was attributed to essentially different aggregational states, depending on the detergent/peptide ratio. The almost linear dependence of the spin-lattice relaxation rate and of the hydrogen-deuterium exchange rate on the fraction of detergent-associated GrS could be reconciled with a simple model, comprising binding of detergent monomers and cooperative binding of micelles at low and high detergent/peptide molar ratios, respectively. Thus, GrS provides a useful model for a study of backbone dynamics and water penetration in detergent- and membrane-bound peptides and proteins. The results will also be discussed with reference to the interaction of GrS with biological membranes. Received: 22 June 1998 / Revised version: 5 October 1998 / Accepted: 9 October 1998