Abstract
Conformational analysis of indomethacin and other nonsteroidal antiinflammatory drugs leads to formulation of a hypothetical complementary receptor site model. The same model can serve to describe the prostaglandin cyclooxygenase active site, and, indeed, arachidonic and other polyunsaturated fatty acids could be folded on the model in a manner which rationalizes their stereospecific transformation to cyclic endo-peroxides (PGG). The model rationalizes the structure-activity relationships of enzyme substrates and inhibitors and appears to be in agreement with biochemical studies of the enzyme.
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