DEVELOPING SELECTIVE CALPAIN INHIBITORS

Donkor博士获得了博士学位。1988年获得学位， 在查佩尔山的北卡罗来纳州大学进行博士后培训 在加入路易斯安那州泽维尔大学（XU）之前， 从1989年到1993年。 在徐他的研究生产力是最低限度的，由于沉重的 教学任务。1993年8月，他加入了大学。 田纳西州（UT）。在UT，有足够的释放时间在他的处置，他有 在两年内发表了五篇同行评审的文章， 那里这清楚地表明。唐可博士对研究的兴趣。他 希望在i）高级药物化学方面发展研究能力 （肽合成，SAR，酶的亲和标记和分子标记） 建模）; ii）分析化学（色谱技术， RP-HPLC、质谱法和凝胶电泳）;和iii）酶学 （蛋白质测定和酶测定）。他将发展这些能力 通过旨在发现有效的选择性抑制剂的实践研究， 钙蛋白酶，这将在未来研究作为抗血栓剂。 凝血酶诱导的血小板聚集在 再闭塞：溶栓治疗或血管成形术治疗 心肌梗塞 已经证明，凝血酶诱导的 血小板聚集是由细胞内活化的 钙蛋白酶在血小板表面通过切割 聚集素，一种推定的ADP受体。选择性钙蛋白酶抑制剂是 因此作为抗血栓形成剂是有意义的。的长期目标 建议的研究是用 开发有效的选择性钙蛋白酶抑制剂的意图， 防止血栓形成的开始和/或传播。的 具体的目的是：i）鉴定活性肽的氨基酸序列， 抑制剂通过亲和标记结合的钙蛋白酶位点;和ii） 合成化合物，使我们能够表征活性位点， 钙蛋白酶

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.