DEVELOPING SELECTIVE CALPAIN INHIBITORS

Donkor博士于1988年获得博士学位，并有一年的 北卡罗来纳大学教堂山分校的博士后培训 在加入路易斯安那州泽维尔大学的教职之前(徐) 到1993年。在徐，他的研究效率很低，因为 教学任务。1993年8月，他加入了芝加哥大学 田纳西州(德克萨斯州)。在德克萨斯大学，有足够的释放时间可以支配，他有 他在两年内发表了五篇同行评议的文章 那里。这清楚地表明。唐科博士对研究的兴趣。他 希望在i)高级药物化学方面发展研究能力 (多肽合成、SAR、酶的亲和标记和分子 建模)；二)分析化学(色谱技术，如 反相高效液相色谱、质谱学和凝胶电泳法)；以及iii)酶学 (蛋白质测定和酶测定)。他将发展这些能力 通过实践研究，旨在发现有效的选择性抑制剂 未来将作为抗血栓药物进行研究。 凝血酶诱导的血小板聚集在 再闭塞后：溶栓治疗或血管成形术 心肌梗死的症状。已经证明凝血酶诱导的 细胞内激活间接介导的血小板聚集 钙蛋白酶通过裂解蛋白在血小板表面表达 聚集素，一种可能的ADP受体。选择性的钙蛋白酶抑制剂是 因此作为抗血栓药物备受关注。中国的长期目标是 建议的研究是用钙蛋白的活性部位 开发有效的钙蛋白酶选择性抑制剂的意图 防止血栓形成的启动和/或传播。这个 具体目标是：i)鉴定活性氨基酸序列 抑制物通过亲和标记结合到的钙蛋白酶的位置；以及ii)到 合成化合物，这将使我们能够表征 钙调蛋白。

Dr. Donkor obtained the Ph.D. Degree in 1988 and had one year of postdoctoral training at the University of North Carolina at Chapel Hill before joining the Faculty at Xavier University of Louisiana (XU) from 1989 to 1993. At XU his research productivity was minimal due to heavy teaching assignments. In August of 1993 he joined the University of Tennessee (UT). At UT, with adequate release time at his disposal, he has published five peer reviewed articles within the two years he has been there. This clearly demonstrates. Dr. Donkor's interest in research. He hopes to develop research capabilities in i) advanced medicinal chemistry (peptide synthesis, SAR, affinity labeling of enzymes, and molecular modeling); ii) analytiCal chemistry (chromatographiC techniques such as RP-HPLC, mass spectrometry, and gel electrophoresis); and iii) enzymology (protein assay, and enzyme assay). He will develop these capabilities through hands-on research aimed at discovering potent selective inhibitors of calpain which will be studied in future as antithrombotic agents. Thrombin-induced platelet aggregation plays an important role in reocclusion following: thrombolytic therapy or angioplasty for treatment of myocardial infarction. It has been demonstrated that thrombin-induced platelet aggregation is indirectly mediated by intracellularly activated calpain expressed on the platelet surface through the cleavage of aggregin, a putative ADP-receptor. Selective calpain inhibitors are therefore of interest as antithrombotic agents. The long-term goal of the proposed research is to characterize the active site of calpain with the intention of developing potent selective inhibitors of calpain for preventing the initiation and/or propagation of thrombus formation. The specific aims are: i) to identify the amino acid sequence at the active site of calpain to which inhibitors bind via affinity labeling; and ii) to synthesize compounds that will allow us to characterize the active site of calpain.