Tuning the Thermodynamic and Kinetic Properties of the Binding of Hairpin Polyamides to Their Cognate DNA Sequences, through Incorporation of Intercalating and Threading Agents

通过掺入嵌入剂和穿线剂来调节发夹聚酰胺与其同源 DNA 序列结合的热力学和动力学特性

• 批准号: 0550992
• 负责人: Moses Lee
• 金额: --
• 依托单位: Hope College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0550992&HistoricalAwards=false
• 关键词: Tuning; Thermodynamic; Kinetic; Properties; Binding

With this new award the Organic and Macromolecular Chemistry Program supports the work of Professor Moses Lee of the Department of Chemistry at Furman University and Professor W. David Wilson of the Department of Chemistry at Georgia State University. The research will involve the synthesis and characterization of hairpin polyamides that bind to DNA in a sequence specific manner. In order to enhance binding to DNA, the sequence specific hairpin polyamide JH-37, previously developed in the PI's lab, will be modified by the incorporation of pendant intercalating and threading groups. These added groups will be chosen for their preference for binding to the minor groove of DNA. Once these compounds are synthesized, the thermodynamics and kinetics of their binding to DNA will be investigated by surface plasmon resonance. Those compounds that exhibit favorable binding constants and kinetics will be examined further by isothermal titration calorimetry and nuclear magnetic resonance. In this way, rational ligand design and synthesis will be linked to the biophysical properties that determine DNA-ligand interactions. These collaborative studies, which will be carried out by undergraduates, graduate students and postdoctorals, will yield information of importance in development of novel biologically active compounds, specific gene knockouts, and gene based biosensors.

通过这一新奖项，有机和高分子化学项目支持弗曼大学化学系的 Moses Lee 教授和佐治亚州立大学化学系的 W. David Wilson 教授的工作。 该研究将涉及以序列特异性方式与 DNA 结合的发夹聚酰胺的合成和表征。 为了增强与 DNA 的结合，PI 实验室先前开发的序列特异性发夹聚酰胺 JH-37 将通过掺入悬挂的嵌入和螺纹基团进行修改。 这些添加的基团将根据其与 DNA 小沟结合的偏好而被选择。 一旦这些化合物被合成，它们与 DNA 结合的热力学和动力学将通过表面等离子共振进行研究。 那些表现出有利的结合常数和动力学的化合物将通过等温滴定量热法和核磁共振进一步检查。 通过这种方式，合理的配体设计和合成将与决定 DNA-配体相互作用的生物物理特性联系起来。 这些合作研究将由本科生、研究生和博士后进行，将为开发新型生物活性化合物、特定基因敲除和基于基因的生物传感器提供重要信息。