STRUCTURAL, KINETIC, AND MECHANISTIC ASPECTS OF CATION COMPLEXATION BY CYCLO-(L-PRO-L-VAL-D-ALA-D-VAL)3

Proton nuclear magnetic resonance studies were carried out on cyclo-(L-Pro-L-Val-D-Ala-D-Val)3(PVAV), a synthetic peptide analogue of the ion transport antibiotic valinomycin. For both the free and cation-complexed forms all resonances were assigned unambiguously, including those of the D- and L-valines where nuclear Overhauser enhancement techniques were used. The latter approach also provided an estimate of the relative internuclear distances between non-spin-coupled proton pairs. In the cation complexes, the peptide backbone is folded into six alternating, hydrogen-bonded, type II ²(1←4) turns (ø2L-Val= -65°; ø2D-Val= +70°; ø3D'Ala= +88°) and has approximate S6 symmetry. The cation is located inside a distorted octahedral cavity formed by the carbonyl oxygens of the valines. The uncomplexed form has C3 symmetry. Its conformation differs from that of the complexes in that the (3 turns formed by the L-Pro-L-Val-D-Ala-D-Val segments are disrupted, while the D-Ala-D-Val-L-Pro-L-Val (3 turns remain intact (øL-Val= —69°; øD-Val= +91°; ΦD_Ala = 85°). Consequently, the entrance to the cation binding site on the proline-valine side is enlarged to provide a pathway for the capture and release of cations. The rate of the peptide-cation dissociation reaction in methanol is slow (kd= 4 X 10-4s-1). It was determined by a novel technique based on deuterium exchange between amides and solvent in mixtures of K+-PVAV and PVAV. © 1979, American Chemical Society. All rights reserved.