Conformational Equilibria in Polypeptides. II. Dihedral-Angle Distribution in Antamanide Based on Three-Bond Coupling Information

Abstract

The use of3Jcoupling information in deriving dihedral-angle restraints for polypeptide-structure determination in the presence of conformational equilibria is illustrated withantamanide,cyclo(–Val1–Pro2– Pro3– Ala4– Phe5– Phe6– Pro7– Pro8– Phe9– Phe10–). The experimental basis comprises accurate three-bond coupling constants as obtained from both homonuclear [C. Griesinger, O.W. Sørensen, and R.R. Ernst,J. Magn. Reson.75,474 (1987)] and heteronuclear [J. M. Schmidt,J. Magn. Reson.124,298 (1997)] exclusive correlation spectroscopy (E.COSY). For the backbone and side-chain dihedral angles in the nonproline residues, φ and χ1, respectively, probability-distribution functions are derived and evaluated on the basis of χ2statistics and significance estimates. Various motional models are considered in the quantitative compilation of molecular-geometry parameters from spin-system parameters. From the3Jcoupling analysis, antamanide is found to possess a very flexible structure which is consistent with the results previously obtained in homonuclear NOE and13C–T1relaxation studies. To fully agree with experiment, rotamer equilibria must be assumed for almost all of the torsions investigated in the peptide.