Molecular basis for prostaglandin potency. III. Tests of the significance of the "hairpin conformation" in biorecognition phenomena

Niels H. Andersen, Shoji Imamoto, N. Subramanian, Donald H. Picker, David W. Ladner, Biswanath De, Sara S. Tynan, Thomas L. Eggerman, L. A. Harker, R. P. Robertson, H. G. Oien, Ch V. Rao

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16 Scopus citations


Prostaglandin analogs of the PGF, 15-epi-PGF, and PGE2 type bearing the following methyl substitution patterns - 15-Me, 16, 16-(Me)2, 17, 17-(Me)2, and 18, 18, 20-(Me)3 - and analogs constrained to "hairpin" alignment [via 1, (ω-1)-olide formation] and to "non-hairpin" arrangements [via 1,9- and 1,15-olide formation] are compared in the following biological assays: contraction of uterine and gastro-intestinal smooth muscle strips, luteolytic antifertility potency in the hamster, binding affinity to two different PGF2α-receptor preparations from bovine corpora lutea, binding to the PGE-specific receptors from rat kidney and liver, inhibition of ADP-induced aggregation of human platelet-rich-plasma, and the effect on rat blood blood pressure. The methylated prostaglandins were also converted to the corresponding prostacyclins and examined as to action on the platelet and on rat blood pressure. All evidence points to topographically distinct receptors for F2α-, E- and I2-type prostaglandins. Cross-reactivity is reduced in most of the analogs examined. Independent of the target organ or tissue, the receptors show common features based on the functional class of PG recognized. "Hairpin" alignment improves binding (and potency) only for the PGF2α specific assays. PGE-specific binding and potency is disrupted to an increasing extent as the chain branching point is moved further from the 15-hydroxyl center. In contrast 16, 16-dimethylation is particularly disruptive for the PGI2/E1platelet receptor interaction.

Original languageEnglish (US)
Pages (from-to)841-856
Number of pages16
Issue number5
StatePublished - Nov 1981
Externally publishedYes

Bibliographical note

Funding Information:
Support for this research has been drawn from National Institutes of Health grant (GM-20848, HL-23103), award (GM-00134), and contract (HD-4-2839, HV-8-2933, HD-8-2808) funds. The authors wish to thank Dr. John Pike for authentic samples of PGE2, PGF2", and some methylated analogs. The studies at the University of Louisville were supported by NIH grant HD-09557. Smooth muscle and hamster antifertility assay results were provided by the Contraceptive Development Branch of the Center for Population Research (NICH & HD).


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