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.
