Costantinos Varotsis

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Tel:      +30-81-393653 -393613
Fax:      +30-81-210951
E-mail:   varotsis@cc.uch.gr

Assistant Professor of Chemisry
B. S in Chemistry and Physics, U. Of Cincinnati, U.S.A 1983
M.S. in Physics, Northeastern Univesity, 1985
Ph. D in Chemical Physics, Michigan State University, 1990
Postdoctoral Fellow 1990-1992, Michigan State University
Fulbright Fellow, 1995-96.

Biophysics of redox metalloenzyme catalysis;time-resolved optical and resonance Raman studies of rapid biological electron transfer reactions; spectroscopy of glycopeptide-derived antibiotics that have been used clinically against cell carcinomas. Antimalarial drugs.

Cytochrome oxidases, a family of heme-copper proteins, catalyse the reduction of O2 in cell respiration which is common to both eukaryotes and aerobic procaryotes. The proteins are isolated in soluble form which allows optical, EPR and resonance Raman spectroscopies to be applied to them. Using these techniques the thermodynamic and structural relationships between the metal components of the enzymes can be studied. Time-resolved optical and resonance Raman spectroscopies are being used to determine the kinetics of electron transfer through the proteins, the effects of oxygen on these electron transfers and the mechanism of oxygen reduction.

The bleomysins (BLM) are a family of glycopeptide-derived antibiotics that have been used clinically against certain malignant lymphomas and squamous cell carcinomas. It has long been known that bleomysin is capable of causing single and double-strand breaks in DNA via a metal-mediated redox mechanism. Bleomysin-madiated DNA degradation requires O2 and a redox active metal ion such as Fe, Cu or Co. Although the formation of activated Fe.BLM involves the reduction of oxygenated Fe(II)BLM, the stoichiometry of O2 consumption or the fate of the oxygen atoms when BLM is activated in the presence or absence of DNA, are not defined. Our goal is to characterize the structure of the O2 intermediates and the mechanism of the Fe.BLM/O2/DNA reaction.

The crystalline substance causing the discoloration of the liver, spleen, and brain, called malaria pigment or hemozoin, is formed within the food vacuoles of intraerythrocytic malaria parasites as a product of the catabolism of hemoglobin. Artemisinin (qinghaosu) is a sesquiterpene endo-peroxide, isolated in 1971 from a Chinese herbal remedy which had been used in the treatment of fevers for over 2000 years. Artemisinin and its derivatives represent an important new class of antimalarial drugs. Other artemisinin derivatives are currently undergoing Phase I and Phase II clinical testing. The antimalarial activity of artemisinin is mediated by a reaction with intraparasitic hemin. In vitro, the reaction between artemisinin and hemin generates organic free radicals which appear to alkylate hemin. The goal of our research is to explore the chemical mechanism of the processes catalyzed by the artemisinin/hemin interaction.

REPRESENTATIVE PUBLICATIONS

1. "Low Power ps Resonance Raman Evidence for Histidine Ligation to Heme a3 after Photodissociation of CO from Cytochrome c Oxidase" Schelvis, H., Varotsis, C., Deinum, G., Ferguson-Miller. S., and Babcock, G.T, J. Am. Chem. Soc., 119, 8409-8416 (1997)

2."Ligand Dynamics in the Binuclear Site in Cytochrome Oxidase" Babcock, G.T, Deinum, G., Hosler, J., Kim, Y., Pressler, M., Proshlyakov, D., Schelvis, H., Varotsis, C., and Ferguson-Miller. S.in Oxygen Homeostasis and Its Dynamics, Y. Ishimura, Ed., Springer-Verlag, Tokyo, 142-150, (1997)

3."Resonance Raman and FTIR Studies of Carbon Monoxide-Bound Cytochrome aa3-600 of Bacillus Subtilis" Varotsis, C. and Vamvouka, M. J. Phys. Chem. in press