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，有机和高分子化学计划支持在弗曼大学化学系教授摩西李和教授W。格鲁吉亚州立大学化学系的大卫·威尔逊说。 该研究将涉及发夹聚酰胺的合成和表征，这些发夹聚酰胺以序列特异性的方式与DNA结合。 为了增强与DNA的结合，先前在PI实验室中开发的序列特异性发夹聚酰胺JH-37将通过引入悬垂嵌入和穿线基团进行修饰。 这些添加的基团将根据它们与DNA小沟结合的偏好来选择。 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进行研究。 那些表现出良好的结合常数和动力学的化合物将进一步研究等温滴定量热法和核磁共振。 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相联系。 这些合作研究将由本科生、研究生和博士后进行，将产生新的生物活性化合物、特定基因敲除和基于基因的生物传感器开发中的重要信息。

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.