Zinc Fingers as Templates for Metal and Metal-DNA Interactions

锌指作为金属和金属-DNA 相互作用的模板

• 批准号: 1058726
• 负责人: Nicholas Farrell
• 金额: $ 46.2万
• 依托单位: Virginia Commonwealth University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2014-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1058726&HistoricalAwards=false
• 关键词: Zinc; Fingers; Templates; Metal; DNA

This research award in the Chemistry of Life Processes (CLP) program supports work by Professor Nicholas Farrell at Virginia Commonwealth University to explore the fundamental chemistry and biology of platinum-metal complexes with zinc finger proteins and model zinc chelates. The proposed work centers on a series of studies pertaining to the coordination chemistry of the so-called zinc fingers, small protein assemblies of zinc ions and a combination of cysteine or histidine residues that play a key role in the structural stability of proteins and other biomolecules such as RNA and DNA. New patterns of zinc-finger chemistry are explored by recognizing the conceptual analogy between alkylation and metallation. These patterns include molecular recognition and electrophilic attack by platinum-metal compounds on zinc-thiolate bonds. Zinc finger proteins are involved in a host of biological processes such as transcription and DNA repair and they are important targets for therapeutic intervention in viral diseases and cancer. The study on the "coordination chemistry" of zinc expands the known properties of this important class of proteins in hitherto unrecognized directions. The research will suggest new mechanisms of action and new targets for biologically active inorganic compounds with long-term possibilities for new medicinal applications. Broader impacts of the project also include the training of undergraduate and graduate students, including joint activities with institutions in Brazil, China, and the Czech Republic.

该生命过程化学 (CLP) 项目的研究奖项支持弗吉尼亚联邦大学 Nicholas Farrell 教授的工作，以探索含锌指蛋白和模型锌螯合物的铂金属络合物的基础化学和生物学。 拟议的工作集中于一系列与所谓的锌指、锌离子的小蛋白质组装体以及半胱氨酸或组氨酸残基的组合的配位化学有关的研究，这些残基在蛋白质和其他生物分子（例如RNA和DNA）的结构稳定性中发挥着关键作用。 通过认识烷基化和金属化之间的概念相似性，探索锌指化学的新模式。 这些模式包括分子识别和铂金属化合物对硫醇锌键的亲电子攻击。 锌指蛋白参与转录和 DNA 修复等一系列生物过程，是病毒性疾病和癌症治疗干预的重要靶点。对锌“配位化学”的研究将这一类重要蛋白质的已知特性扩展到迄今为止尚未认识的方向。 该研究将为生物活性无机化合物提出新的作用机制和新靶点，并为新的医学应用提供长期的可能性。 该项目更广泛的影响还包括本科生和研究生的培训，包括与巴西、中国和捷克共和国机构的联合活动。