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

FEBS Letters

Atkinson, R.Andrew¹  Pelton, John T.¹ 

[1]Marion Merrell Dow Research Institute, 16 rue d'Ankara, 67084 Strasbourg, France

关键词: Endothelin;    Nuclear magnetic resonance;    Circular dichroism;    Conformation;    Molecular modeling;    FMOC;    fluorenylmethoxy carbonyl;    FAB-MS;    Fast atom bombardment-mass spectroscopy;    CD;    Circular dichroism;    NMR;    Nuclear magnetic resonance spectroscopy;    DQF COSY;    2-D Double quantum filtered correlated spectroscopy;    TOCSY;    2-D totally correlated spectroscopy;    NOESY;    2-D nuclear Overhauser enhancement spectroscopy;    ROESY;    rotating frame NOESY;    ppm;    parts per million;    Standard 3-letter abbreviations for the amino acids;    are used throughout;   

DOI  :  10.1016/0014-5793(92)80390-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 β type II turn and a γ′ turn.

【 授权许可】

Unknown