Solution conformation of Endothelin-1 by 1H NMR,CD, and molecular modeling

The solution conformation of Endothelin-1, a recently discovered bicyclic, 21 amino acid peptide, has been examined by ¹H NMR in deuterated dimethylsulphoxide and circular dichroism in aqueous and organic solvents. A total of 158 NOES were detected, which were used as distance constraints in the distance geometry program DISGEO. Two families of structures were obtained, both characterized by a helix-like region extending from Lys⁹ to Cys¹⁵, but with opposite “handedness”. Circular dichroism studies of the peptide in both aqueous and trifluoroethanol solutions show a negative shoulder at 224 nm, characteristic of right-handed helices. Molecular dynamics and energy minimization yielded a solution structure for this new peptide compatible with all experimental observations.