ENZYME IMMOBILIZATION FOR REMOVAL OF TOXIC METABOLITES

用于去除有毒代谢物的酶固定化

• 批准号: 3495824
• 负责人: SHAWN G DUNKIRK
• 金额: $ 5万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3495824
• 关键词: alkaline phosphatase; arginase; biomedical equipment development; chemical synthesis; covalent bond; detoxification; enzyme mechanism; enzyme substrate; enzyme therapy; immobilized enzymes; inborn metabolism disorder; metabolism disorder chemotherapy; photolysis; radiotracer; reagent /indicator; spectrometry; thermodynamics; urease

Enzyme deficiencies associated with inborn metabolic defects are usually fatal within the first few years of life. Treatments such as diet manipulation, gene replacement therapy, chemotherapy, transfusions, transplantations, and peritoneal dialysis have produced marginal improvements in these patients. Enzyme replacement therapy is an appealing alternative or adjunct to these treatments. However, direct enzyme replacement has led to hypersensitivity responses in the hosts, and instability of such preparations has made use of such procedures impractical. We propose to explore immobilization chemistries for development of enzyme-activated surfaces for extracorporeal removal of toxic metabolites. We will use photochemical procedures to activate support matrices for subsequent coupling to the model enzyme, arginase. Successful demonstration of the improved enzyme activities afforded by this technology in an in vitro blood system will lead to continuation of this project with a consultant laboratory for Phase II animal model studies.

与先天性代谢缺陷相关的酶缺乏症 通常在生命的最初几年内致命。等治疗 如控制饮食，基因替代疗法，化疗， 输血、移植和腹膜透析 对这些患者的治疗效果并不明显 酶 替代疗法是一种有吸引力的替代疗法或辅助疗法， 治疗。 然而，直接酶替代导致了 在宿主中的超敏反应，以及这种超敏反应的不稳定性， 制备使得使用这些程序不切实际。 我们 建议探索固定化化学品， 用于体外清除有毒物质的酶活化表面 代谢物。 我们将使用光化学程序来激活 用于随后偶联至模型酶的支持基质， 放轻松 改良酶的成功示范 该技术在体外血液系统中提供的活性 将导致该项目继续与顾问 用于II期动物模型研究的实验室。