Technology for isolation of Integrase Inhibitors for Therapeutics against Human I

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AI084610-01
Agency Tracking Number: AI084610
Amount: $599,602.00
Phase: Phase I
Program: SBIR
Awards Year: 2009
Solicitation Year: 2009
Solicitation Topic Code: N/A
Solicitation Number: PHS2009-2
Small Business Information
DUNS: 828972765
HUBZone Owned: Y
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (801) 583-2787
Business Contact
Phone: (801) 581-7792
Research Institution
DESCRIPTION (provided by applicant): Currently there are 40 million people estimated to be infected with HIV/AIDS worldwide; 22 million people have died since its discovery in 1980's. Drugs inhibiting the reverse transcriptase (RT), protease, and integrase - three essential enzymes for the replication and propagation of HIV in the host - are available. However, viral resistance and drug side effects necessitate development of new treatments for HIV/AIDS. One target among these three may prove to have further drugable domains. Although in vitro screens for inhibitory drugs against HIV integrase (INT) have been difficult due to its low aqueous solubility and propensity toward protein aggregation, we have discovered an inhibitory peptide against INT using a yeast two hybrid assay. The peptide has a unique mode of action than the current strand transfer inhibitors. This inhibitory peptide in conjunction with yeast two hybrid technology may lend itself to a screening platform resulting in the discovery of novel inhibitory compounds of INT. The goal of the proposed research is to obtain a small molecule that mimics the mechanistic effects of a peptide inhibitor of HIV INT. Briefly, the specific aims are 1) to optimize target-peptide displacement assays; 2) to screen chemical libraries under high throughput conditions for compounds that disrupt peptide-HIV INT interaction in yeast; and 3) to select the best candidates for screening. PUBLIC HEALTH RELEVANCE: The proposed research describes methods to isolate novel drugs that inhibit HIV integrase, an essential enzyme in the replication cycle of this devastating virus. Compounds isolated that possess desirable inhibitory properties will be optimized for further pre-clinical studies.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government