STRUCTURAL INVESTIGATIONS OF MODE OF ACTION OF DRUGS

本研究计划的目标是（i）阐明 理化性质与化学结构的关系 要研究的药物，以及（ii）也要了解确切的分子 这些药物抑制核酸和蛋白质合成的机制。 选择用于这些研究的药物是蒽环类，例如阿克拉霉素， 诺加霉素、斯替菲霉素等;利福霉素; DNA的共价结合剂，例如 蒽霉素、西比罗霉素、托马霉素、新丝霉素等;米托蒽醌; 环肽抗生素，例如棘霉素、ostreogrycin、放线菌素， 等等;核苷类抗生素，例如谷氏菌素、尼可霉素;以及 抗肿瘤多肽抗生素。 此外，这些药物与 将研究核酸和蛋白质的片段。 的方法 用于调查将主要是X射线晶体学，核磁共振， 计算机制图. 这些调查的结果将有助于揭示 这些药物与靶分子相互作用的位点， 可以假定药物-受体相互作用的模型。 还有， 可以假设对药物结构的修饰可以增强 他们的治疗选择性

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.