The 3-dimensional structure of anticancer drug-DNA complexes determined by X-ray crystallography

X射线晶体学测定抗癌药物-DNA复合物的三维结构

• 批准号: nhmrc : 107228
• 负责人: E/Pr Jules Guss
• 金额: $ 17.63万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/3-dimensional-structure-ray-crystallography/101193
• 关键词: dimensional; structure; anticancer; drug; DNA

Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents act by poisoning the DNA binding enzyme topoisomerase. Crystallographic analysis will give us unequivocal answers at the atomic level as to the exact way in which the drug binds to DNA and how this binding differs between antitumour active and inactive compounds. We believe that a knowledge of the DNA binding mode of a class of intercalating anticancer drugs at the atomic level is valuable in guiding drug design within that class.

我们的主要目标是发现抗癌药物如何与DNA相互作用的分子细节，以及这些相互作用与非活性化学相关化合物的相互作用如何不同。我们建议使用X射线晶体学与我们已经开发的用于确定一类抗肿瘤活性药物的DNA复合物的三维结构的成功方法一起研究其他临床或科学上重要的DNA嵌入抗癌药物的复合物。这些试剂通过毒化DNA结合酶拓扑异构酶而起作用。晶体学分析将在原子水平上为我们提供明确的答案，即药物与DNA结合的确切方式以及这种结合在抗肿瘤活性化合物和非活性化合物之间的差异。我们认为，一类嵌入抗癌药物在原子水平上的DNA结合模式的知识是有价值的，在该类药物设计的指导。