The benzoisochromanequinones (BIQs) are a family of aromatic polyketides of which members have been found to possess significant biological activities including selective inhibition of the anti-cancer target farnesyltransferase (FTase), toxicity to tumor cells in both in vitro and in vivo assays, and inhibition of multi-drug resistant and susceptible strains of bacteria. Much is now known about the polyketide genes and proteins responsible for the biosynthesis of these compounds, and we propose to construct a library of novel BIQ analogs through metabolic engineering and combinatorial biosynthesis. We intend to evaluate these analogs for activity against multi-drug and susceptible strains of Staphylococcus aureus, a fibroblast and K- 562 leukemia cell line, and FTase and geranylgeranyltransferase I enzymes. The results from screening the BIQ library in this panel would allow evaluation of the selectivity of the various compounds and the identification of any BIQ analogs with superior bioactivity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA115079-01
Application #
6933282
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Lohrey, Nancy
Project Start
2005-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$42,068
Indirect Cost
Name
Stanford University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305