Fluorescent Nucleosides and Oligonucleotides with New Capabilities

具有新功能的荧光核苷和寡核苷酸

• 批准号: 2102642
• 负责人: Byron Purse
• 金额: $ 48万
• 依托单位: San Diego State University Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102642&HistoricalAwards=false
• 关键词: Fluorescent; Nucleosides; Oligonucleotides; New; Capabilities

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Byron Purse of San Diego State University is seeking to develop a deep understanding of the relationship between chemical structure, local molecular environment, and fluorescent properties of nucleobase analogues, synthetic building blocks for DNA and RNA. These fluorescent nucleobase analogues (FBAs) are an important class of molecular probes, used to understand the biochemical mechanisms that control gene expression and the maintenance and copying of the genetic code. Designing fluorescent molecular probes for these applications is challenging and the capabilities of FBAs are limited because it is not yet possible to predict how their fluorescence will change when the probes are placed in a biological context. Integral to this research is a plan to train graduate students who will lead the laboratory work and participate in all aspects project planning, data analysis, interpretation, collaborations, and the dissemination of results. The involvement of undergraduate researchers is included, as is a Course-based Undergraduate Research Experience (CURE) in the SDSU Physical Chemistry Lab to further broaden participation.This project has three specific technical objectives: (1) to develop fluorescent nucleobase analogues (FBAs) with high brightness and photostability and assess their performance in fluorescence studies of nucleic acids at the single-molecule level; (2) to develop the ability of pairs of FBAs to measure short and long-range structure and dynamics simultaneously using spectral feature analysis and FRET and (3) to develop a theoretical approach to understanding FBA photophysics and responses to local environment using a combination of new analogue design and synthesis, fluorescence studies, and computation. The research supported by this project seeks to measure and understand how fluorescence changes when FBAs are placed in differing contexts in DNA and RNA and use this understanding, together with synthetic organic chemistry, to create new fluorescent probes with enhanced capabilities to accelerate discovery.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在这个由化学系化学结构、动态和机制B计划资助的项目中，圣地亚哥州立大学的拜伦·普斯教授正在寻求深入了解核碱基类似物的化学结构、当地分子环境和荧光性质之间的关系，核碱基类似物是DNA和RNA的合成构件。这些荧光碱基类似物(FBA)是一类重要的分子探针，用于了解控制基因表达以及遗传密码的维持和复制的生化机制。为这些应用设计荧光分子探针是具有挑战性的，而且FBAs的能力也是有限的，因为目前还不可能预测当探针放置在生物环境中时，它们的荧光将如何变化。这项研究的组成部分是一项培养研究生的计划，他们将领导实验室工作，并参与项目规划、数据分析、解释、合作和结果传播的所有方面。该项目包括本科生研究人员的参与，以及SDSU物理化学实验室基于课程的本科生研究经验(CURE)，以进一步扩大参与范围。该项目有三个具体的技术目标：(1)开发具有高亮度和光稳定性的荧光核苷酸类似物(FBAs)，并在单分子水平上评估它们在核酸荧光研究中的表现；(2)发展FBA对利用光谱特征分析和FRET同时测量短程和长程结构和动力学的能力；(3)发展一种通过新的模拟设计和合成、荧光研究和计算相结合的理论方法来理解FBA的光物理和对局部环境的响应。该项目支持的研究试图测量和了解当FFA放置在DNA和RNA的不同环境中时荧光的变化，并利用这种理解，与合成有机化学一起，创造具有增强能力的新荧光探测器，以加速发现。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。