Inhibition of prostaglandin endoperoxide synthetase by thiol analogues of prostaglandin.

Authors:
  • SOS Ohki
    S Ohki
  • NON Ogino
    N Ogino
  • SYS Yamamoto
    S Yamamoto
  • OHO Hayaishi
    O Hayaishi
  • HYH Yamamoto
    H Yamamoto
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Abstract
A variety of thiol compounds inhibited the enzymatic bis-oxygenation of 8,11,14-eicosatrienoic acid to prostaglandin G1 [PGG1] as examined with a purified preparation of PG endoperoxide synthetase (PG synthase; 8,11,14-eicosatrienoate, H-donor:Ox oxidoreductase; EC 1.14.99.1) from bovine vesicular gland. The hydroperoxide cleavage of PGG1 producing PGH1 was not affected by these thiol compounds. Several PG analogues with a thiol group (9,11-dihydroxy-15S- or 15R-mercaptoprosta-5,13-dienoic acid, 1-mercapto-9,11,15-trihydroxyprosta-5,13-diene and 1-mercapto-9-oxo-11,15-dihydroxyprosta-5,13-diene) were most potent inhibitors, showing almost complete inhibition at concentrations on the order of 1 .mu.M. Other thiol compounds, such as 2,3-dimercaptopropanol, dithiothreitol and dihydrolipoic acid, were inhibitory but were much less effective. The inhibition, as examined with 9,11-dihydroxy-15S-mercaptoprosta-5,13-dienoic acid and 2,3-dimercaptopropanol, was noncompetitive.

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