The objectives of this research program are (i) to elucidate the relationship between physicochemical properties and chemical structures of the drugs to be studied, and (ii) also to understand the exact molecular mechanism by which these drugs inhibit nucleic acid and protein synthesis. The drugs chosen for these studies are Anthracyclines, e.g. aclacinomycin, nogalamycin, steffimycin, etc.; Rifamycins; Covalent binders of DNA, e.g. anthramycin, sibiromycin, tomaymycin, neothramycin, etc.; Mitoxantrones; Cyclic peptide antibiotics, e.g. echinomycin, ostreogrycin, actinomycin, etc.; Nucleoside antibiotics, e.g. gougerotin, nikkomycin; as well as Antitumor polypeptide antibiotics. Also, complexes of these drugs with fragments of nucleic acids and proteins will be investigated. The methods used for investigations will be mainly X-ray crystallography, NMR, and computer graphics. The results of these investigations will help reveal the sites of interaction of these drugs to the target molecules and thus models for drug-receptor interaction can be postulated. Also, modifications to the structures of the drugs can be postulated to enhance their therapeutic selectivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032690-06
Application #
3281719
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1983-04-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Pharmacy
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713