STRUCTURAL INVESTIGATIONS OF MODE OF ACTION OF DRUGS

药物作用方式的结构研究

• 批准号: 3281721
• 负责人: SATISH K ARORA
• 金额: $ 13.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281721
• 关键词: X ray crystallography; anthracyclines; antibiotics; bleomycin; chemical models; chemical structure function; doxorubicin; drug interactions; drug metabolism; drug receptors; metal complex; mitomycin C; mitomycins; nuclear magnetic resonance spectroscopy; nucleic acid inhibitor; protein biosynthesis; rifamycins

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.

该研究计划的目标是 (i) 阐明 理化性质与化学结构之间的关系 要研究的药物，以及（ii）还要了解确切的分子 这些药物抑制核酸和蛋白质合成的机制。 这些研究选择的药物是蒽环类药物，例如蒽环类药物。阿克拉霉素， 诺加霉素、斯特菲霉素等；利福霉素； DNA 的共价结合物，例如 蒽霉素、西伯霉素、茅霉素、新霉素等；米托蒽醌； 环肽抗生素，例如棘霉素、骨霉素、放线菌素、 ETC。;核苷类抗生素，例如古格罗汀、尼可霉素；也 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。 方法 用于研究的主要是X射线晶体学、NMR和 计算机图形学。 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，从而 可以假设药物-受体相互作用的模型。 还， 可以假设对药物结构的修饰可以增强 他们的治疗选择性。