Conformationally restricted analogs of oxytocin; stabilization of inhibitory conformation

MICHAL LEBL, PATRICIA HILL, WIESLAW KAZMIERSKI, LENKA KÁRÁSZOVÁ, JIŘINA SLANINOVÁ, IVO FRIČ, VICTOR J. HRUBY

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Analogs of oxytocin containing tetrahydroisoquinoline carboxylic acid (Tic) of L or D configuration in position 2 were synthesized and their biological activities were tested. Both analogs showed negligible agonist activity in uterotonic, galactogogic, and pressor assays, but they are in vitro uterotonic inhibitors. In comparison with oxytocin analogs containing l‐ or D‐phenylalanine in position 2, the analog with the D‐configuration of the conformationally fixed aromatic residue has significantly increased inhibitory activity which suggests that the proper conformation for the interaction with the receptor, but not for its activation, was stabilized. 1H NMR and CD studies, supported by theoretical calculations, suggest that the conformational properties of the analog containing D‐tetrahydroisoquinoline carboxylic acid are similar to those of [2D‐phenylalaninejoxytocin.

Original languageEnglish (US)
Pages (from-to)321-330
Number of pages10
JournalInternational journal of peptide and protein research
Volume36
Issue number4
DOIs
StatePublished - Oct 1990

Keywords

  • NMR
  • circular dichroism
  • conformation
  • conformational constraint
  • oxytocin inhibitors

ASJC Scopus subject areas

  • Biochemistry

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