The capacity of structurally modified analogs of prostaglandin F2α (PGF2α) to inhibit binding of [3H]PGF2α 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]PGF2α 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 PGF2α receptor. Several phenyl-substituted analogs exhibited receptor-binding potency greater than or equal to native PGF2α, while most other analogs had reduced capacity to compete with native PGF2α for binding. Several 17-azidophenol PGF2α 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-PGF2α as well as 17-(3-iodo-4-azidophenyl)-18,19,20-trinor-PGF2α exhibited binding affinities that were approximately 10% of native PCF2α, and the radioiodinated analogs of PGF2α may be useful as probes of the PGF2α receptor.
|Number of pages||7|
|State||Published - Jul 15 1989|
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