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Research Interests: Protein Nephrotoxicity
Using a coupling technique to (1) study physiological mechanisms and (2) to improve biologically active proteins toward a better therapeutic agent.
Proteins with molecular weight less than 70,000 dalton are readily filtered through the kidneys and lost in urine, resulting in a very short half-life in the plasma. Coupling this kind of proteins to an inert macromolecule like dextran can effectively increase the molecular size and prevent renal clearance, leading to a much longer plasma half-life. For example, it has been a long time dream that doctors can use hemoglobin as a blood substitute for transfusion. However hemoglobin is just small enough to be filtered through the kidney and the short plasma half-life imposes great limitation on its use. Coupling hemoglobin to dextran prolongs its half-life and make it a more promising blood substitute. Another example is trichosanthin (MW 26,000) which is a potential anti-AIDS agent that also falls into this category of having short plasma half-life. Again, coupling to dextran increases it by several times.
Coupling dextran to hemoglobin or trichosanthin makes them non-filtering into the renal tubule. Making use of this property, the coupled products are used to explore the nephrotoxic mechanism caused by these proteins. Recently we are studying the effects of steric hindrance on the protein at the site of its attachment. By genetic engineering, this coupling site can be directed at any location of the protein molecule. The effect of steric hindrance on antigenicity and cell entry at various sites of the protein molecule can then be studied.
Selected Publications:
* Tam, Siu-Cheung, Bluemnstein, Jan & Wong, J. Tze-Fei (1976) Soluble dextran-hemoglobin complex as a potential blood substitute. Proc. Natl. Acad Sci. USA 73(6),2128-2131.
* Tam, Siu-Cheung & Wong, J.T. (1988) Impairment of renal function by stroma-free hemoglobin in rats. J Lab. Clin. Med I 1 1(2), 189-193.
* Ko, W.H., Wong, C.C., Yeung, H.W., Yung, M.H., Shaw, P.C. & Tam, S.C. (1991) Increasing the plasma half-life of trichosanthin by coupling to dextran. Biochemical Pharmacology 42(9), 1721-1728.
* Cheng, T.S., Ko, W.H., Swaininathan, R. & Tam, S.C. (1992) The effect of lysine on hemolysis induced renal damage. J Lab. Clin. Med 119(5), 496-502.
* Ko, W.H., Wong, C.C., Yeung, H.W., & Tam, S.C. (1992) Modulation of trichosanthin antigenicity by coupling to dextran. Biochemistry International 28(4), 643-650.
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