The development of potent peptide agonists and antagonists for the endothelin receptors.
The endothelins (ETs), sarafotoxins (SRTXs), vasoactive intestinal contractor (VIC), and bibrotoxin are a family of potent vasoconstrictor peptides. All peptides in this family possess 21 amino acids arranged in a unique bicyclic motif formed between cystine bridges in the 1-15 and 3-11 positions. Since the discovery of endothelin-1 (ET-1) in 1988, significant effort has been focused on the understanding of its structure-activity relationships. The identification of endothelin receptor subtypes has led to the discovery/design of potent peptide agonists and antagonists, along with nonpeptide antagonists of endothelin with varying levels of potency and receptor subtype selectivity. In keeping with the theme of this journal, this review will focus only on the development of peptidic-based agonists and antagonists of endothelin in addition to their applications in understanding the physiological and/or pathophysiological role of endothelin and its isopeptides.
Cody
W L
WL
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Doherty
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D016232:Endothelins / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D017466:Receptors, Endothelin / Q000819:agonists*; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry; D014757:Viper Venoms / Q000737:chemistry
D016232:Endothelins; D010455:Peptides; D017466:Receptors, Endothelin; D014757:Viper Venoms; D014660:Vasoactive Intestinal Peptide