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

有了这个新的奖项，有机和高分子化学项目支持了弗曼大学化学系的摩西·李教授和佐治亚州立大学化学系的W·大卫·威尔逊教授的工作。这项研究将涉及以序列特异的方式与DNA结合的发夹状聚酰胺的合成和表征。为了增强与DNA的结合，之前在PI的实验室开发的序列特异性发夹聚酰胺JH-37将通过加入侧基插层和穿线基团进行修饰。这些添加的基团将根据它们与DNA的小槽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体共振来研究。那些表现出良好的结合常数和动力学的化合物将进一步通过等温滴定、量热法和核磁共振进行检测。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性质联系在一起。这些合作研究将由本科生、研究生和博士后进行，将产生对开发新的生物活性化合物、特定的基因敲除和基于基因的生物传感器具有重要意义的信息。

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.