The long term goals of this research are characterization of the nature of DNA relaxation by eukaryotic DNA topoisomerase I at a molecular level and identification of those parameters of topoisomerase I inhibition that are critical for the expression of anti-tumor activity. This should permit the identical of second generation topoisomerase I inhibitors suitable for development as anti-tumor agents. For the period of requested support, the specific aims include better definition of the nature of inhibitor binding by the topoisomerase I-DNA covalent binary complex, the identification of an optimal system for studying topoisomerase I-DNA interaction at high resolution and exploration of the possible role of other cellular factors in the expression of cytotoxicity by topoisomerase I inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078415-04
Application #
6624676
Study Section
Special Emphasis Panel (ZRG1-BNP (03))
Program Officer
Fu, Yali
Project Start
1999-12-23
Project End
2003-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
4
Fiscal Year
2003
Total Cost
$195,007
Indirect Cost
Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Rahier, Nicolas J; Cheng, Kejun; Gao, Rong et al. (2005) Synthesis of 14-azacamptothecin, a water-soluble topoisomerase I poison. Org Lett 7:835-7
Rahier, Nicolas J; Eisenhauer, Brian M; Gao, Rong et al. (2004) Water-soluble camptothecin derivatives that are intrinsic topoisomerase I poisons. Org Lett 6:321-4

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