STRUCTURAL INVESTIGATIONS OF MODEL ACTION OF DRUGS

药物作用模型的结构研究

• 批准号: 3281717
• 负责人: SATISH K ARORA
• 金额: $ 7.21万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281717
• 关键词: X ray crystallography; bleomycin; chemical models; chemical structure function; doxorubicin; drug interactions; drug metabolism; gramicidin; mitomycin C; mitomycins; nuclear magnetic resonance spectroscopy; nucleic acid inhibitor; rifamycins

The objectives of the research program are (i) to elucidate the relationship between physiochemical properties and chemical structures of the drugs, and (ii) also to understand the exact molecular mechanism by which these drugs inhibit nucleic acid and protein synthesis. The drugs chosen for studies are rifamycin SV, rifamycin S, holomycins, nogalamycins, adriamycins, aclacinomycin, steffimycin, anthramycin, sibiromycin, tomaymycin, neothramycin, gramicidins, virginiamycin, astreogrycin, chromomycin, olivomycin, echinomycin, bleomycin, bouvardins, edeines, and mitomycins. Also complexes of these drugs with fragments of mucleic 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 investigation 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.

研究计划的目标是(I)阐明 香豆素的理化性质与化学结构的关系 药物，和(Ii)也了解确切的分子机制 这些药物抑制核酸和蛋白质的合成。这些药物 选择进行研究的有利福霉素SV、利福霉素S、全息霉素、新霉素、 阿霉素、阿克拉霉素、斯特菲霉素、安息香素、西比罗霉素、 托美霉素、新甲状霉素、革兰菌素、维吉尼亚霉素、阿司匹林、 色霉素、橄榄霉素、棘霉素、博莱霉素、布伐他丁、依地奈德和 丝裂霉素类。也包括这些药物与核酸片段的络合物 并对蛋白质进行研究。用于调查的方法 将主要是X射线结晶学、核磁共振和计算机图形学。这个 这些调查的结果将有助于揭示 这些药物以靶分子为靶标，从而为药物受体模型 相互作用是可以假定的。另请参阅对 可以假定药物可以增强它们的治疗选择性。