Date of Award

7-1-1981

Degree Type

Thesis

University or Center

Atlanta University (AU)

Degree Name

M.S.

Department

Biology

First Advisor

Dr. Cyril L. Moore

Second Advisor

Dr. Philip Needleman

Abstract

The use of acetylenic acid analogues differing in chain length or position of the triple bond permitted the systematic study of structural activity relationships for both the arachidonate metabolizing enzymes (i.e., cyclooxygenase and lipoxygenase) in platelets and the relationship of the enzyme to aggregation. Analogues were found that preferentially inhibited: a) cyclooxygenase only; b) 12-lipoxygenase only (HETE); c) both the cyclooxygenase and lipoxygenase; d) neither enzyme in platelets. There was a direct correlation between the rank order of potency of the acetylenic analogues to inhibit platelet cyclooxygenase and to suppress aggregation. Certain structural features of the triynoic acetylenic analogues were critical in influencing platelet function; thus, the presence of a triple bond at position 14 as well as the lack of the triple bond at position 5 resulted in a compound that inhibited both cyclooxygenase and platelet aggregation. Analogues that inhibited the platelet 12-lipoxygenase but not the CO. were very weak inhibitors of platelet aggregation. These acetylenic acid analogues provide potentially powerful tools for dissociating the two arachidonate metabolic pathways and if other tissues are as readily manipulated as platelets, the analogues could be especially useful to gain insight into the contribution of lipoxygenase products to other biological functions.

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