26.12.2001, 16:41 ), a novel antihypertensive ® (with Drs. T. Rosenthal (with and E. Peleg, Drs. T. (with Drs. A. D.Haratz, Shaish and A. ke prevents arterial plaque formation in genetically genetically in formation plaque arterial prevents ke 8256 Allyl mercaptocaptopril (Captosal mercaptocaptopril Allyl Allicin upta generate conjugates -mAb anti-cancer therapy: Novel Allicin is toxic to various cancer cell lines. Allicin short half-life Allicin for soil fumigation in greenhouses and crop protection of Man t with Captopril, commonly used as a hypotensive drug that that drug hypotensive a as used antilipidemic drug and commonly TAU-Med). Allicin lowers blood pressure and triglycerides in hypertensive and hyperlipidemic rats . The reaction of allicin Captopril, with contains free SH, yielded quantitative amounts of a novel compound This allyl-mercaptocaptopril. compound, stable and lowered blood pressure and triglycerides in hypertensive rats at smaller doses (2-fold) than those used for Captopril. models mice modified Gonen, TAU-Med). Allicin was found to bind to serum LDL fraction and to inhibit its subsequent uptake macrophages. by allicin of Apo-E to administration oral Daily LDL- or knockout mice caused a dramatic reduction in the formation of plaques. arterial coronary sites. allicin target at itsprevents use in Conjugates vivo. consisting of pure alliinase ligated to a mAb specific for cancer marker ErbB2 retain their specific receptor recognition and enzymatic activity. Addition of the alliin to conjugate-treated cell culture generates normal damaging without cells target which the kills allicin, experiments Preliminary receptor. mAb the of devoid cells in mice clearly demonstrated the high anti-tumor activity of the conjugates (Fig. 2) (animal experiments done M with Dr. Mironchik). (with Drs. I. Chet and M. Abramski, HUJ-Agri). Methyl bromide has been recently banned from use as a soil fumigating agent 972 8 946 Fax. 3808 [email protected] [email protected] 972 8 934 Tel. E-mail: Department of Biological Chemistry Department Allicin from and its and its garlic from Allicin for applications numerous benefi the Allicin specifically reacts with 202 Most of the available garlic capsules contain Synthesis of allicin from alliin from allicin of Synthesis C for months (Fig. 1). Allicin is the main biologically active molecule in crushed solutions. aqueous allicin in pure of production Continuous Thiol-modifying activity of allicin. Binary capsules generate pre-determined doses of allicin in o free thiol groups of numerous proteins, resulting in inactivation inactivation in resulting proteins, numerous of groups thiol free of a variety of such as papain, caspases, ACE, and alcohol dehydrogenases. Allicin also reacts with free thiol-containing molecules such as glutathione to yield allylmercaptoglutathione. Objectives of Research of Objectives garlic. Our objective is to investigate ifpure Allicin can be useful for the treatment of various human diseases as well as for environmental and agricultural uses. The main problems which we aim to overcome stemand short life time from of allicin. This requires the development of the very high reactivity,unique delivery systems and chemical stabilization studies. sensitivity findings Recent Allicin is produced due to the interaction of the garlic , alliinase, with the substrate alliin. Alliinase was isolated, enabling thus matrix, solid a to coupled and chemically stabilized efficientthe nature-identical synthetic, of conversion to alliin allicin. Aqueous solutions of allicin can be stored in the cold at 4 the small intestine. small the amountsvery of allicin. small, if any, A binary entero-coated predetermined of consisting prepared recently capsule was amounts of alliinase and alliin, which physically are kept separateda special by formulation. When the ingested capsules the with interacts and dissolves alliin intestine, small the reach allicin. of amount predictable a produce to alliinase Fig. 1 Fig. Talia Miron Talia Aharon Rabinkov Mirelman David Meir Wilchek Meir

]202 meir_wilchek meir_wilchek Rabinkov, A., Miron, T., Mirelman, D., Wilchek, M., Glozman, M., Glozman, T., D., Miron, Wilchek, Rabinkov, A., Mirelman, Weiner, and M. T., D.,Miron, Wilchek, Mirelman, Rabinkov, A., H., Mirelman, D., D.,Levkovitz, S., Harats, Gavri, Abramovitz, T., D., Miron, Weiner, and Mirelman, L. Rabinkov, A., M., Wilchek, L., T., Miron, Rabinkov, A., Konstantinovski, Mirelman, M., and T., S., Miron, Wilchek, Ankri, Rabinkov, A., Selected Publications nematodes. and fungi as such pathogens soil from plants toprotect shown been has toseeding prior ofallicin doses low with ofsoil ozone layer. the on Irrigation effect toits due Fig. 2 with glutathione possesses SH-modifying and antioxidant antioxidant and SH-modifying possesses glutathione with The of reaction product allicin S-Allylmercaptoglutathione: S., Yavin, Weiner, E., (2000) and L. biological activity. Biochem. Biophys. Acta 1463, 20-30. through phospholipid membranes may contribute to its permeability ready its ofallicin: ofaction mode The (2000) L. 10, Dis. 515-519. Art. Coron. diet. rich cholesterol with fed mice in (atherosclerosis) formation streak fatty in Eldar, M., and Vered, (1999) Z. reduction induced Allicin M., T.,D., Miron, Wilchek, S., Eilat-Adar, Rabinkov, A., 317-325. 265, Biochem. Anal. thiosulfinates. with nitro-5-thiobenzoate of Reaction 2-allicin and alliinase lyase) (alliin activity: Wilchek, M. (1998) A spectrophotometric assay for containing proteins. Biochem. Biophys. Acta 1379, 233-244. thiol with interaction and Trapping ofradicals of Allicin: ofaction mode The D. Weiner, (1998) and L. Mirelman, 41, &Chemother. Agents 2286-2288. Antimicrob. histolytica. ofEntamoeba effects cytopathic and proteinases D. (1997) Allicin from garlic strongly inhibits cysteine Monoclonal -alliinase conjugates for anticancer therapy. 203 Elkayam, A., Mirelman, D., Peleg, E., Wilchek, M., Miron, Miron, M., D., E., Wilchek, Peleg, Mirelman, A., Elkayam, Y., M., Giat, T., Danilenko, K., Miron, Rabinkov, A., Hirsch, and Yedaand Institute. Weizmann Co. Ltd.atthe Acknowledgements M.W. holds the Marc R. Gutwirth Chair of Molecular Biology. ofMolecular Chair Gutwirth M.W. R. Marc the holds Center Levine the from by grants supported was research The Hypertension 14,Hypertension 377-381. hyperinsulinemic hyperlipidemic hypertensive rats. Am. J. fructose-induced in Enalapril and ofAllicin effects The T. Rosenthal, (2001) T., S., and Sadetzki, Rabinkov, A., 245-254. 38, Nutr. &Cancer proliferation. cell cancer on ofgarlic, ingredient a major of allicin, effect The Y. M., Levy, Sharoni, J., and (2000) Wilchek, properties. Biochim. Biophys. Acta 1499, 144-153.

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Molecular Basis of Disease