AMP-KINASE CASCADE ACTIVATORS AND ATHEROGENESIS

AMP-激酶级联激活剂和动脉粥样硬化

• 批准号: 3502263
• 负责人: J FOULKES
• 金额: $ 4.98万
• 依托单位: OSI PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3502263
• 关键词: adenylate kinase; antihypercholesterolemic agent; atherosclerosis; chromatography; drug design /synthesis /production; enzyme inhibitors; enzyme structure; enzyme substrate; phosphorylation; protein purification

DESCRIPTION (Adapted from Applicant's Abstract):Myocardial and cerebral infarction, conditions which are primarily the result of atherosclerotic lesions within coronary and cerebral blood vessels, are the leading causes of death in Western civilization. A causal link between hypercholesterolemia and the premature development of atherosclerosis is well established. Hepatic biosynthesis is responsible for the majority of cholesterol transported in plasma lipoprotein. The rate limiting enzyme of cholesterol biosynthesis, HMGCoA reductase, is therefore a prime target for drug intervention. HMGCoA reductase is regulated by a bicyclic protein kinase cascade, the AMP-activated protein kinase cascade.It is the aim of this project to develop a purification scheme for the AMP-activated kinase with the ultimate goal being to develop a high throughput screen to discover compounds to activate the kinase kinase and thereby amplify the cascade. The Phase I of the project will identify a suitable source for enzyme purification and develop an enzyme based assay. Cell based assays will be developed and the enzyme cloned in Phase II.

描述（改编自申请人的摘要）：心肌和大脑 梗塞，主要是动脉粥样硬化的结果 冠状动脉和脑血管内的病变是主要原因 西方文明的死亡。 之间的因果关系 高胆固醇血症和动脉粥样硬化的过早发展是 良好。 肝生物合成负责大多数 胆固醇在血浆脂蛋白中运输。 限制率的酶 因此，胆固醇生物合成，HMGCOA还原酶是 药物干预。 HMGCOA还原酶由双环蛋白调节 激酶级联AMP激活的蛋白激酶级联反应。 这个项目是为AMP激活激酶开发纯化方案 最终目标是将高吞吐量屏幕开发到 发现化合物激活激酶激酶，从而扩大 级联。 该项目的第一阶段将确定适合的来源 酶纯化并开发基于酶的测定法。基于细胞的测定 将开发并在II期中克隆酶。