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

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.