title: Molecular modelling of the structures of endothelin antagonists. Identification of a possible structural determinant for ET-A receptor binding.
abstract: Computer-aided molecular modelling of the endothelin (ET-A) receptor antagonists, BQ-123 and BE-18257B, shows that they have very similar 3D structures. Parts of their 3D structures are also shown to match closely with that reported for residues 6-8 in endothelin-1. On the basis of these similarities (and with supporting evidence from literature data on endothelin structure-activity relationships) a structural determinant is proposed for ET-A receptor binding, and novel designs of peptide are suggested for providing more potent and selective ET-A receptor antagonists.
authors.affiliation: Department of Pharmacy, King's College London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: D
authors.initials: D
authors.lastname: Barlow
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin
chemical_list: D016232:Endothelins; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C069764:cyclo(glutamyl-alanyl-isoleucyl-leucyl-tryptophyl); C072247:cyclo(Trp-Asp-Pro-Val-Leu)