Towards Functional Metal-Mediated DNA Base-Pairs

迈向功能性金属介导的 DNA 碱基对

• 批准号: 1310423
• 负责人: Christopher Switzer
• 金额: $ 40万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1310423&HistoricalAwards=false
• 关键词: Towards; Functional; Metal; Mediated; DNA

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Christopher Switzer at the University of California-Riverside, to develop metal mediated base pairs that are capable of participating in information transfer reactions alongside their natural counterparts. To accomplish this objective, metal mediated base pair motifs will be developed with optimal shape and size for acceptance by natural enzymes. The work under the award will build on preliminary studies by the PI's laboratory to create a next generation metal mediated base pair capable of such function. This next generation base pair uses a tridentate purine-like component and a monodentate pyrimidine-like component to coordinate a divalent metal ion, such as Cu2+. The function of metal mediated base pairs with natural polymerase enzymes will be explored and optimized by employing a range of different monodentate nucleotides chosen on the basis of synthetic expediency and known optimal design features.Watson-Crick base pairs encode genetic information in all organisms. While natural base pairs rely on hydrogen bonds for recognition, other weak or reversible interactions hold promise for the creation of non-standard base pairs. Metal-mediated bonds have been shown recently to replace hydrogen bonds between non-standard bases in the DNA helix. The next steps in the progression to achieve functional metal-mediated base pairs are therefore now within reach. The program of study will provide a solid training ground for graduate students in chemical biology. Additionally, research opportunities for undergraduate students will be offered during the proposal period, including a summer undergraduate research position for underrepresented minorities or women.

通过此奖项，化学生命过程的化学过程计划正在为加利福尼亚大学河畔大学的克里斯托弗·斯威策博士提供资金，以开发能够与自然对应物一起参与信息传输反应的金属介导的碱基对。为了实现这一目标，将开发金属介导的碱基对基序，其形状和大小为天然酶接受。该奖项下的工作将基于PI实验室的初步研究，以创建能够具有此类功能的下一代金属介导的碱基对。下一代的碱基对使用三齿的嘌呤状成分和单张嘧啶样的成分来协调二价金属离子，例如Cu2+。通过使用合成的权宜之计和已知的最佳设计特征选择的一系列不同的单次单次核苷酸，将探索和优化金属介导的碱基对与天然聚合酶的功能。Watson-Crick Base Pairs对所有生物体中的遗传信息编码遗传信息。尽管自然碱基对依靠氢键来识别，但其他弱或可逆的相互作用却有望创建非标准的碱基对。最近已经显示了金属介导的键，以替代DNA螺旋中非标准碱基之间的氢键。因此，进展的下一步以实现功能性金属介导的碱基对。研究计划将为化学生物学研究生提供扎实的培训理由。此外，在提案期间还将提供针对本科生的研究机会，包括针对代表性不足的少数民族或妇女的夏季本科研究职位。