This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-1 protease (HIV PR) is an aspartic protease that is essential for the life-cycle of HIV. HIV PR cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious. Thus, mutation of HIV PR's active site or inhibition of its activity disrupts HIV's ability to replicate and infect additional cells, making HIV PR inhibition the subject of much pharmaceutical research. High Field ESR studies were undertaken of HIV PR in order to better resolve flap dynamics of the PR in inhibited and non-inhibited forms, using a variety of popular spin labels. Of the spin labels tried, MTSL showed resolvable differences in the flap dynamics of inhibited and non-inhibited forms of HIV PR at 240 GHz. At lower frequencies, none of the spin labels allowed resolution of a difference in flap dynamics. Given that the 240 GHz results using MTSL allow one to resolve details of the flap dynamics, and thus act as a 'fingerprint'for effective HIV PR inhibition or non-inhibition, further studies on drug-resistant strains and different inhibitors at 240 GHz are planned.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR016292-09
Application #
7956689
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2009-09-01
Project End
2010-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
9
Fiscal Year
2009
Total Cost
$17,774
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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