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Bright and responsive fluorescent nucleosides from structure-photophysics relationships

来自结构-光物理关系的明亮且响应性荧光核苷

基本信息

批准号：
1709796
负责人：
Byron Purse
金额：
$ 13万
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：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709796&HistoricalAwards=false
关键词：
Bright responsive fluorescent nucleosides structure

项目摘要

In this project funded by the Chemical Structure, Dynamics and Mechanisms B Program of the Chemistry Division, Professor Byron Purse of the Department of Chemistry and Biochemistry at San Diego State University is developing next-generation fluorescent nucleosides as tools for studying nucleic acids. In addition to storing the genetic code, nucleic acids have many important regulatory roles in gene expression and metabolism. Fluorescent nucleosides are chemically modified building blocks of nucleic acids that are widely used in biophysical studies aimed at understanding the regulation of gene expression. This project aims to enhance the understanding of the relationship between structure and fluorescence properties of these nucleoside probes, and to use this knowledge to add new capabilities to the toolkit of fluorescent nucleoside analogues. Integral to the research plan is the studying of the fluorescence properties of these new nucleoside analogues in the Physical Chemistry teaching laboratory of San Diego State University and an outreach program targeting high school and community college students in the computational work.The rational design of fluorescent nucleoside analogues with specifically targeted properties is a great challenge because predicting photo-physical properties based on structure, especially in a complex environment like a nucleic acid duplex, is difficult to achieve. In this project, photophysical studies coupled with density functional theory methods are being used to establish structure-photophysics relationships, in order to develop next-generation fluorescent nucleosides with desired fluorescence properties. The desired fluorescence properties include: (a) large fluorescence turn-on responses to base stacking (i.e. 100-fold), (b) brightness matching conventional fluorophores, sufficient to enable single-molecule biophysics and tracking of labeled nucleic acids by fluorescence microscopy, and (c) analogues that absorb and emit at the red end of the visible spectrum.

在这个由化学学部化学结构、动力学和机制B项目资助的项目中，圣地亚哥州立大学化学和生物化学系的Byron Purse教授正在开发下一代荧光核苷作为研究核酸的工具。除了储存遗传密码外，核酸在基因表达和代谢中具有许多重要的调节作用。荧光核苷是一种化学修饰的核酸构建模块，广泛用于旨在了解基因表达调控的生物物理研究。该项目旨在加强对这些核苷探针的结构和荧光特性之间关系的理解，并利用这些知识为荧光核苷类似物的工具包添加新的功能。研究计划的组成部分是在圣地亚哥州立大学的物理化学教学实验室研究这些新的核苷类似物的荧光特性，并在计算工作中针对高中和社区大学的学生进行扩展计划。合理设计具有特异性靶向性质的荧光核苷类似物是一项巨大的挑战，因为基于结构预测光物理性质，特别是在核酸双相这样的复杂环境中，很难实现。在这个项目中，光物理研究结合密度泛函理论方法被用来建立结构-光物理关系，以开发具有所需荧光特性的下一代荧光核苷。所需的荧光特性包括：(a)对碱基堆叠的大荧光开启响应（即100倍），(b)与传统荧光团匹配的亮度，足以通过荧光显微镜实现单分子生物物理学和标记核酸的跟踪，以及(c)在可见光谱的红端吸收和发射的类似物。