Vol. 153, No. 1, 1988 May 31, 1988 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 479-486 AJOENE INHIBITION OF PLATELET AGGREGATION : POSSIBLE MEDIATION BY A H~OPROTEIN Moideen P. Jamaluddin, Lissy K. Krishnan & Ancy Thomas Thrombosis Research Unit, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrtun-695012, INDIA Received April 29, 1988 SUMMARY. AJoene, an organosulfur compound derived from garlic, was found by spectral measurements, to interact, cooperatively, with a purified hemoprotein implicated, previously, in platelet activation. It modified the binding interactions of the protein with ligands, deemed to be physiologically relevant as effectors. The characteristics of the modifications were found to parallel those of aJoene induced modifications of agonist-induced aggreg- ation kinetics of gel-filtered calf platelets. © z988 Aoademic P .....~nc INTRODUCTION. AJ oene, (E, Z) -4, 5, 9-trithiadodeca-l, 6,11-triene 9-oxide, derived from garlic, irreversibly inhibits platelet aggregation without affecting shape-change, metabolism of endo- genous arachidonate, cAMP levels, and protein phosphorylation (1-4). Recent evidence suggests its mechanism of action to be by direct interaction with the fibrinogen receptor of platelets (4). This mechanism, however, fails to explain the apparent cooperati- vity of its inhibitory action (4)o Therefore an additional or alternative site of action is suggested. We have implicated ligand-induced conformational change of a dimeric hemoprotein in platelet activation (5,6). Here we report on a parallelism found between the modifying effects of aJoene on ligand binding to this protein and the modifications it effected on the kinetics of agonist-lnduced aggregation of calf platelets° MATERIALS AND METHODS. AJoene was purified from freshly peeled, crushed, garlic employing an adaptation of published procedures (2). The purified compound was kept dissolved in 0.13 M NaC1, at -30"C. H209 was a product of Glaxo (India). Other chemicals were from c~mmercial sources given before (5,7-9). Gelfiltered platelets (GFP) were prepared as described (7-9) except for the following modifications : acid-citrate-dextrose solution replaced trisodium citrate as anticoagulant (1.5 ml per 8.5 ml of blood) 479 0006-291X/88 $1.50 Copyright © 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.