Structural requirements for prostaglandin analog interaction with the ovine corpus luteum prostaglandin F receptor. Implications for development of a photoaffinity probe

Anil K. Balapure, Caird E. Rexroad, Kenji Kawada, David S. Watt, Tony A. Fitz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The capacity of structurally modified analogs of prostaglandin F (PGF) to inhibit binding of [3H]PGF to receptors on ovine luteal cells was evaluated by radioreceptorassay using dispersed, viable, ovine luteal cells. Binding assays were conducted at pH 5.75, since binding to both high (Kd 17.4 ± 2.3 nM) and low (Kd 409 ± 166 nM) affinity sites was enhanced markedly at reduced pH. The capability to compete with [3H]PGF for binding was evaluated for different prostaglandin analogs having modifications in the C-8 "upper" side-chain, in the cyclopentane ring, or in the C-12 "lower" side-chain. Prostaglandin J2 was a surprisingly potent competitor for binding to the PGF receptor. Several phenyl-substituted analogs exhibited receptor-binding potency greater than or equal to native PGF, while most other analogs had reduced capacity to compete with native PGF for binding. Several 17-azidophenol PGF analogs were synthesized and tested, but analogs having hydroxyl groups on the aryl ring had low affinity for receptors. However, 17-(4-azidophenyl)-18,19,20-trinor-PGF as well as 17-(3-iodo-4-azidophenyl)-18,19,20-trinor-PGF exhibited binding affinities that were approximately 10% of native PCF, and the radioiodinated analogs of PGF may be useful as probes of the PGF receptor.

Original languageEnglish
Pages (from-to)2375-2381
Number of pages7
JournalBiochemical Pharmacology
Volume38
Issue number14
DOIs
StatePublished - Jul 15 1989

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint

Dive into the research topics of 'Structural requirements for prostaglandin analog interaction with the ovine corpus luteum prostaglandin F receptor. Implications for development of a photoaffinity probe'. Together they form a unique fingerprint.

Cite this