STRUCTURAL INVESTIGATIONS OF MODE OF ACTION OF DRUGS

本研究计划的目的是(i)阐明

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.