[Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity

Biochem Biophys Res Commun. 1991 Aug 30;179(1):286-92. doi: 10.1016/0006-291x(91)91367-l.


A linear peptide analog of endothelin (ET)-1, [Ala1,3,11,15]ET-1 (4AlaET-1), and its truncated peptide analogs were synthesized to study the structural requirements of ET-1 for the recognition of ETs-nonselective ETB receptors. ET-1 exhibited sub-nanomolar binding to two distinct ET receptor subtypes (ETA and ETB), but 4AlaET-1 bound to ETB with an affinity 1,700 times higher than that seen during binding to ETA. The truncated linear peptides 4AlaET-1(6-21), 4AlaET-1(8-21) and N-acetyl-4AlaET-1(10-21) still had high affinity for ETB, whereas 4AlaET-1(6-20) and 4AlaET-1(11-21) displayed remarkably reduced affinity for ETB. Therefore, ET-1 requires the Glu10-Trp21 sequence for ETB binding, but not the disulfide bridges. These ETB-binding peptides elicit endothelium-dependent vasorelaxation of porcine pulmonary arteries in parallel with the binding affinity for ETB, suggesting that they are ETB agonists.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta / metabolism
  • Binding, Competitive
  • Cell Membrane / metabolism
  • Cerebellum / metabolism
  • Endothelins / chemical synthesis*
  • Endothelins / metabolism
  • Endothelins / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism*
  • Receptors, Endothelin
  • Structure-Activity Relationship
  • Swine
  • Vasodilation / drug effects


  • Endothelins
  • Peptides, Cyclic
  • Receptors, Cell Surface
  • Receptors, Endothelin
  • endothelin 1, Ala(1,3,11,15)-