Oxytocin antagonists with changes in the Asn5 position shed light on hormone‐oxytocin receptor interactions

PATRICIA S. HILL, W. Y. CHAN, VICTOR J. HRUBY

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Since oxytocin agonists and antagonists have different structure‐activity relationships, we have investigated the stereostructural and stereoelectronic requirements of the Asn5 residue in oxytocin antagonists by the synthesis of four analogues of the potent, prolonged acting oxytocin antagonist [Pen1,d‐Phe2,Thr4,Orn8]‐oxytocin (I) in which Asn5 was replaced respectively with Thr (II), Leu5 (III), Asp5 (IV) and Tyr5 (V). These analogues had pA2 values in the antioxytocic in vitro rat uterine assay of 7.23 (I), 7.16 (II), 6.67 (III), 7.21 (IV), and 6.76 (IV), respectively. All were also found to be weakly potent in the in vivo anti‐vasopressor assay in the rat. These studies demonstrate very different structural and stereoelectronic requirements for oxytocin agonists and antagonists when they interact with the oxytocin uterine receptor.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalInternational journal of peptide and protein research
Volume38
Issue number1
DOIs
StatePublished - Jul 1991

Keywords

  • oxytocin
  • oxytocin antagonists
  • oxytocin inhibitors
  • stereoelectronic requirements of oxytocin
  • structure activity of peptide antagonists

ASJC Scopus subject areas

  • Biochemistry

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