In vitro and in vivo enzyme studies of polyhemoglobin-tyrosinase.
Melanoma is now the fifth most common type of cancer in North America. At present, there is no optimal treatment for this cancer. However, the lowering of the tyrosine level can inhibit the growth of melanoma. Unfortunately, this diet restriction cannot be humanly tolerated and causes vomiting, nausea, and severe body weight loss. To prevent these problems, we are studying a new approach involving the preparation intermolecularly crosslinked hemoglobin and tyrosinase for intravenous injection. In this article we describe the method of preparation and the structural and functional properties of polyhemoglobin-tyrosinase. We evaluate the effects of varying glutaraldehyde ratio, crosslinking time, and enzyme concentration on the enzyme activity of polyhemoglobin-tyrosinase. We also optimize the molecular weight distribution of polyhemoglobin-tyrosinase. The stability of polyhemoglobin-tyrosinase at 37 degrees C is much more stable when compared to noncrosslinked tyrosinase solution. Animal studies show that a higher degree of polymerization correlates with a longer circulation time of polyhemoglobin-tyrosinase, and the optimal crosslinking time is 24 hours. One intravenous injection of polyhemoglobin-tyrosinase lowers the plasma tyrosine to about 10% of its original level within one hour.
Yu
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Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada H3G 1Y6.
Chang
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TM
D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D001776:Blood Circulation Time; D003432:Cross-Linking Reagents / Q000737:chemistry; D004795:Enzyme Stability; D006454:Hemoglobins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007275:Injections, Intravenous; D008545:Melanoma / Q000378:metabolism / Q000628:therapy; D014442:Monophenol Monooxygenase / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D000447:Aldehydes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; C491833:polyhemoglobin-tyrosinase; D014443:Tyrosine; C007860:glutaconaldehyde; D014442:Monophenol Monooxygenase