Viral proliferation and most cellular functions require the interaction of regulatory proteins with their cognate recognition sequences. We wish to identify small molecules that will interfere with these DNA:protein interactions by binding in a sequence-specific manner to the DNA recognition site. DNA-binding molecules may have extremely broad applications as antiviral, anticancer, or antimicrobial drugs. Immunosuppression and cardiovascular diseases are other potential targets for DNA-binding molecules. We have developed a high-throughput screening assay for detecting DNA-binding molecules. The assay is designed to determine the relative affinity of these molecules for virtually any short DNA sequence and can be used to screen large libraries of crude biological mixtures or synthetic chemicals for the presence of novel sequence-specific DNA-binding molecules. In addition, the assay is capable of determining the sequence-specificity of known DNA-binding drugs. In Phase II, we propose to screen known DNA-binding molecules to determine the highest affinity binding sites for each molecule among 256 4-base pair binding sites. These data will be used to design congeners directed to specific critical DNA target sites in viral genomes and medically significant target sites in the human genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44AI028633-02
Application #
3506112
Study Section
Special Emphasis Panel (SSS (B))
Project Start
1990-09-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Genelabs Technologies, Inc.
Department
Type
DUNS #
City
Redwood City
State
CA
Country
United States
Zip Code
94063