NMR studies on DNA interactions of polynuclear platinum

多核铂DNA相互作用的NMR研究

• 批准号: ARC : LX0346972
• 负责人: Nicholas Farrell
• 金额: $ 3.2万
• 依托单位: The University of Western Australia
• 依托单位国家: 澳大利亚
• 项目类别: Linkage - International
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/nmr-studies-dna-polynuclear-platinum/64908
• 关键词: NMR; studies; DNA; interactions; polynuclear

NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur nucleophiles will aid in understanding their metabolism and toxicity. The results of this work will aid in the selection of back-up clinical candidates and the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.

多核铂DNA相互作用的核磁共振研究。BBR3464是一类结构独特的铂类抗癌药物的代表，目前正在进行临床试验。抗癌活性很可能取决于与DNA的结合，但其机制与广泛使用的药物顺铂不同。本项目使用核磁共振波谱法详细跟踪DNA加合物的逐步形成。进一步扩展多核铂配合物与硫亲核试剂的反应将有助于了解它们的代谢和毒性。这项工作的结果将有助于选择后备临床候选药物，并设计针对特定DNA序列的药物，用于新的基因治疗。