Reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is a multifunctional enzyme that serves as major target for the development of drugs to treat infection with this virus. Both DNA polymerase and ribonuclease H (RNase H) activities are essential for conversion of the single-stranded RNA genome into double-stranded DNA. However, all clinically used RT inhibitors are directed against the polymerase active site of the enzyme, while drugs that block specifically RNase H activity have yet to be developed. The primary goal of this proposal is to establish novel tools for the study of RNase H inhibition. We have previously developed site-specific footprinting techniques that allow us to precisely determine the position of HIV-1 RT on its primer/template substrate. We will further explore this technology in order to study changes in the trajectory of the bound nucleic acid substrate. We hypothesize that compounds that bind specifically to the RNase H domain can induce such changes that produce an unfavorable interaction between the enzyme and its RNA substrate. ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI065316-01A2
Application #
7166726
Study Section
AIDS Discovery and Development of Therapeutics Study Section (ADDT)
Program Officer
Conley, Tony J
Project Start
2006-08-01
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$207,500
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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