Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
基本信息
- 批准号:RGPIN-2017-06683
- 负责人:
- 金额:$ 3.28万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2019
- 资助国家:加拿大
- 起止时间:2019-01-01 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are the central molecules of life. The discovery of the double helix structure of DNA, described by Watson and Crick over 60 years ago, continues to lead to numerous advances in biology and medicine. More recently, this elegant structure and the nature of its specific interactions have inspired scientists and engineers to investigate technological applications for nucleic acids. Through organic synthesis, modification of the nucleic acid scaffold can be achieved leading to molecules with increased functionality for a broad range of applications that can improve our society.******One avenue of nucleic acid based research that our group will explore involves investigation of the relationship between modification/damage to the information content of DNA with the response of DNA repair proteins. The importance of DNA repair was endorsed by the scientific community with the 2015 Nobel Prize in Chemistry awarded to Lindahl, Modrich and Sancar for their contributions to our understanding of DNA repair pathways. Our laboratory has been interested in exploring the ability of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) to act upon on a variety of modified nucleic acid structures prepared by organic synthesis. AGTs can remove alkylation damage from the O6-atom of 2'-deoxyguanosine and O4-atom of thymidine with differences in repair efficiency towards these lesions depending on the source of the AGT (i.e. Human versus E. coli). To address this issue, we will explore the influence of various groups at the C5-position of thymidine on AGT repair. We will also explore AGT repair of intrastrand cross-link lesions in G-quadruplex structures. These findings will enhance our knowledge of substrates that AGT, a protein important for health and growing applications in biotechnology, can process. Our group will study the processing of DNA damage by bypass polymerases with chemically synthesized analogs of DNA damage resulting from reactive nitrogen species and investigate the influence of nucleobase orientation on nucleotide incoportation. Understanding the mechanisms by which these proteins bypass damage provides important insights explaining why some forms of damage offer such a challenge for the cell to repair. We will study ways to stabilize the parallel stranded duplex formed by polyadenosine, a structure that is of interest for applications in nucleic acid nanoscience. Also, we will develop methods for incorporation of selenium into nucleic acids to add to the toolbox of methods for structure determination by X-ray crystallography.******Canada has a very active and growing research community in the field of nucleic acid chemistry. This research program will provide multidisciplinary training in the fields of organic chemistry and biochemistry to the next generation of scientists embarking in this important field of science.
脱氧核糖核酸(DNA)和核糖核酸(RNA)是生命的中心分子。60多年前,沃森和克里克描述了DNA双螺旋结构的发现,这一发现继续推动着生物学和医学的许多进步。最近,这种优雅的结构及其特定相互作用的性质启发了科学家和工程师研究核酸的技术应用。通过有机合成,可以实现对核酸支架的修饰,从而使分子具有更多的功能,从而改善我们的社会。我们小组将探索的基于核酸的研究的一个途径是调查DNA信息含量的修饰/破坏与DNA修复蛋白的反应之间的关系。DNA修复的重要性得到了科学界的认可,2015年诺贝尔化学奖授予Lindahl、Modrich和Sancar,以表彰他们对我们对DNA修复途径的理解做出的贡献。本实验室一直致力于探索DNA修复蛋白O6-烷基鸟嘌呤-DNA烷基转移酶(AGT)对有机合成制备的各种修饰核酸结构的作用能力。AGTS可以去除2‘-脱氧鸟苷的O6-原子和胸苷的O4-原子的烷基化损伤,这些损伤的修复效率因AGT的来源而异(即人与大肠杆菌)。为了解决这个问题,我们将探索胸腺嘧啶核苷C5位上的不同基团对AGT修复的影响。我们还将探索AGT修复G-四链结构中的链内交叉连接损伤。这些发现将加强我们对AGT底物的了解,AGT是一种对健康和生物技术日益增长的应用非常重要的蛋白质,可以加工。我们的团队将研究旁路聚合酶对DNA损伤的处理,使用化学合成的由活性氮物种引起的DNA损伤的类似物,并研究核苷酸碱基取向对核苷酸合成的影响。了解这些蛋白质绕过损伤的机制可以提供重要的见解,解释为什么某些形式的损伤会给细胞修复带来如此大的挑战。我们将研究稳定多聚腺苷形成的平行链双链的方法,这是一种在核酸纳米科学中有应用价值的结构。此外,我们还将开发将硒结合到核酸中的方法,以增加X射线结晶学结构确定方法的工具箱。*加拿大在核酸化学领域拥有非常活跃和不断增长的研究社区。这项研究计划将为从事这一重要科学领域的下一代科学家提供有机化学和生物化学领域的多学科培训。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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{{ truncateString('Wilds, Christopher', 18)}}的其他基金
Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2022
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2021
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Urgent Replacement of a Biomolecular Imager For Bioorganic and Biological Chemistry Research
紧急更换用于生物有机和生物化学研究的生物分子成像仪
- 批准号:
RTI-2021-00470 - 财政年份:2020
- 资助金额:
$ 3.28万 - 项目类别:
Research Tools and Instruments
Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2020
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2018
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2017
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Synthesis and investigation of modified oligonucleotides as probes of DNA repair
作为 DNA 修复探针的修饰寡核苷酸的合成和研究
- 批准号:
299384-2011 - 财政年份:2016
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Synthesis and investigation of modified oligonucleotides as probes of DNA repair
作为 DNA 修复探针的修饰寡核苷酸的合成和研究
- 批准号:
299384-2011 - 财政年份:2014
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
Synthesis and investigation of modified oligonucleotides as probes of DNA repair
作为 DNA 修复探针的修饰寡核苷酸的合成和研究
- 批准号:
299384-2011 - 财政年份:2013
- 资助金额:
$ 3.28万 - 项目类别:
Discovery Grants Program - Individual
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Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
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Modified Nucleic Acid Structures to Interrogate Biochemical Processes and Design Principles of Responsive Nanodevices
修饰核酸结构以探究响应性纳米器件的生化过程和设计原理
- 批准号:
RGPIN-2017-06683 - 财政年份:2017
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