The role of the disulphide bonds in endothelin-1.
The smooth muscle contracting peptide endothelin-1 is characterized by the presence of two disulphide bonds and their importance for maintaining the agonist activity of the peptide was examined by synthesizing analogues of endothelin-1 lacking one or the other, or both, of these bonds. The circular dichroic spectra of these analogues (in which alanine residues replaced the appropriate cystines), [Ala1,15]-, [Ala3,11]- and [Ala1,3,11,15]-endothelin-1 had features in common with that of endothelin-1. All three analogues exhibited at least some agonist activity in guinea-pig isolated trachea, but surprisingly endothelin-1 was a partial agonist in comparison with the analogue [Ala3,11]endothelin-1. The disulphide bonds are therefore not absolutely essential for maintaining the tertiary structure necessary for agonist activity at endothelin-1 receptors in all tissues.
Merrell Dow Research Institute, Strasbourg, France.
J T
JT
Pelton
R C
RC
Miller
D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides; D016232:Endothelins / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014132:Trachea
D004220:Disulfides; D016232:Endothelins