Synthesis and solution conformation of c(D-Trp-D-Cys(SO3-Na+)-Pro-D-Val-Leu), a potent endothelin-A receptor antagonist

Int J Pept Protein Res. 1993 Aug;42(2):194-203. doi: 10.1111/j.1399-3011.1993.tb00496.x.

Abstract

The endothelin family of polypeptides are known to exert potent physiological effects which include cardiovascular regulation. The solution conformation and dynamics of c(D-Trp-D-Cys(SO3-Na+)-Pro-D-Val-Leu), a potent endothelin-A receptor-selective antagonist, were characterized in aqueous solution by NMR spectroscopy and molecular modeling. NMR-derived conformational constraints were combined with computer-assisted molecular modeling using distance geometry calculations and energy minimization. The pentapeptide backbone is shown to adopt a single conformation in solution comprising a type II beta-turn and an inverse gamma-turn, with each residue in the trans conformation. Molecular dynamics were explored using relaxation measurements and low-temperature studies, and indicate that the peptide backbone is highly constrained with little conformational mobility present.

MeSH terms

  • Amino Acid Sequence
  • Computer Simulation
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Peptides, Cyclic / chemistry*
  • Solutions

Substances

  • Peptides, Cyclic
  • Solutions
  • cyclo(sulfoalanyl-prolyl-valyl-leucyl-tryptophyl)