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Conformational study of cyclo[D‐Trp‐D‐Asp‐Pro‐D‐Val‐Leu], an endothelin‐A receptor‐selective antagonist
Author(s) -
Atkinson R.Andrew,
Pelton John T.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80390-3
Subject(s) - chemistry , stereochemistry , hydrogen bond , acetonitrile , nuclear magnetic resonance spectroscopy , peptide , cyclic peptide , endothelin receptor , residue (chemistry) , receptor , antagonist , solvent , two dimensional nuclear magnetic resonance spectroscopy , molecule , biochemistry , organic chemistry
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.