Publication Year

1997

Keywords

Chemistry, structure, non-steroidal, anti-inflammatory, drugs

Disciplines

Chemistry | Organic Chemistry | Physical Sciences and Mathematics

Abstract

Prostaglandin endoperoxide H synthase-1 and 2 (PGH-1 and 2) are the enzymes that catalyze the rate-determining reaction of the conversion of arachidonic acid to prostaglandin, the main mediator of inflammatory reactions and pain. Members of the non-steroidal anti-inflammatory drugs (NSAID) family have been shown to have inhibitory effects on both of these enzymes with varying characteristics. NSAID's currently available in the market, however, were designed and developed in large part without the crystal structure of PGH-2. Research has shown that PGH-2 is the producer of prostaglandins that mediate inflammation, while PGH-1 serves as a "housekeeping" enzyme regulating gastrointestinal and renal function. Current painkillers, while stopping the production of pain and inflammation-causing prostaglandins also inhibit those that regulate gastric mucosa and renal function. Research has shown, however, that PGH-1 and 2 are differentially sensitive to pharmacological agents with certain molecules inhibiting one of the two isozymes specifically. This study seeks to identify structural parameters that are important in the binding of those PGH-2-selective molecules to the active site of PGH-2. It is hoped that these findings may be used in the design of the new generation of NSAID's which are selective towards PGH-2 and eliminate ulcerogenic and nephrotoxic properties of current NSAID's.

Department 1 Awarding Honors Status

Chemistry

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