Conformational study of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], an endothelin-A receptor-selective antagonist.

The conformation of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], (BQ123), an endothelin-A receptor-selective antagonist, has been studied in 20% acetonitrile in water by CD and NMR spectroscopy. CD studies showed the peptide adopted a similar, constrained conformation in both water alone and 20% acetonitrile in water. NMR spectra showed the proline residue to be in the trans conformation and 2 of the NH protons to exchange slowly with the solvent, indicating hydrogen bonding. Structural constraints derived from the NMR spectra were used to define the conformation in molecular dynamics simulations. A single backbone conformation is observed for the cycle, comprising a beta type II turn and a gamma' turn.