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.

有了这个奖项，化学部的生命过程化学计划正在资助加州大学河滨分校的Christopher Switzer博士，以开发能够与天然对应物一起参与信息传递反应的金属介导的碱基对。为了实现这一目标，金属介导的碱基对基序将被开发为具有最佳形状和大小以供天然酶接受。该奖项下的工作将建立在PI实验室的初步研究基础上，以创建具有这种功能的下一代金属介导的碱基对。这种下一代碱基对使用三齿嘌呤样组分和单齿嘧啶样组分来配位二价金属离子，例如Cu 2+。金属介导的碱基对与天然聚合酶的功能将被探索和优化，通过采用一系列不同的单齿核苷酸的基础上选择的合成方便和已知的最佳设计feature.Watson-Crick碱基对编码在所有生物体的遗传信息。虽然天然碱基对依赖于氢键进行识别，但其他弱或可逆的相互作用有望产生非标准碱基对。金属介导的键最近已被证明可以取代DNA螺旋中非标准碱基之间的氢键。因此，在实现功能性金属介导的碱基对的进展中的下一个步骤现在是触手可及的。该研究计划将为化学生物学研究生提供坚实的培训基础。此外，在提案期间将为本科生提供研究机会，包括为代表性不足的少数民族或妇女提供夏季本科生研究职位。