THERMODYNAMICS OF DNA CONFORMATION AND INTERACTIONS

DNA 构象和相互作用的热力学

• 批准号: 6018771
• 负责人: LUIS ARNALDO MARKY
• 金额: $ 18.6万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6018771
• 关键词: DNA; RNA; calorimetry; chemical hydration; circular dichroism; conformation; densitometry; interferometry; intermolecular interaction; nucleic acid chemical synthesis; nucleic acid structure; thermodynamics; ultraviolet spectrometry; DNA; RNA; calorimetry; chemical hydration; circular dichroism; conformation; densitometry; interferometry; intermolecular interaction; nucleic acid chemical synthesis; nucleic acid structure; thermodynamics; ultraviolet spectrometry

DESCRIPTION: This is a renewal application for an existing grant. This proposal aims to measure complete thermodynamic profiles including hydration effects for a variety of DNA duplexes, some with modified phosphates, and for a number of DNA or DNA/RNA duplexes with intercalated or covalently bound ligands. Experimental methods include temperature and pressure dependent UV and CD spectroscopy, high sensitivity differential scanning calorimetry, and titration calorimetry. In particular, Dr. Marky proposes: 1) to characterize the role of counterions (Cs+ ,Na+ , K+ , Mg++) in the stability of telomeric and centromeric model sequences. 2) to determine the overall hydration of hairpins (stem-loop structures) containing bulges and mismatches and to characterize hydration effects from interactions with intercalating agents. Complete thermodynamics profiles (deltaG, deltaH, delta S and deltaV) will be obtained. 3) to determine differences in thermodynamic behavior, including hydration, of DNA, RNA and mixed duplexes. 4) to thermodynamically characterize, in terms of binding mode and conformation, the hydration effects from placing covalently bound hydrophobic moieties in oligomer duplexes. 5. to obtain complete thermodynamic profiles, including heat capacity effects, for side-by-side binding of cross-linked lexitropsins to the minor groove of DNA. 6. to determine the electrostatic and hydration contributions in the formation of DNA bent structures.

描述：这是现有赠款的续签申请。 这 提案旨在衡量完整的热力学特征，包括水合 各种DNA双链体的效果，有些具有改良的磷酸盐和 对于多个DNA或DNA/RNA双链体，具有插入或共价 结合配体。 实验方法包括温度和压力 依赖的紫外线和CD光谱，高灵敏度差异扫描 量热法和滴定量热法。 特别是，Marky博士建议： 1）表征对抗（CS+，Na+，K+，Mg ++）的作用 端粒和中心模型序列的稳定性。 2）确定 装有凸起和 不匹配并表征与与之相互作用的水合效应 插入剂。 完整的热力学轮廓（Deltag，Deltah， 将获得Delta s和deltav）。 3）确定差异 DNA，RNA和混合双链体的热力学行为，包括水合。 4）以结合模式和 构象，水合效果共价结合 疏水部分在寡聚双链体中。 5。获得完整 并排的热力学轮廓，包括热容量效应 交联的词汇素与DNA的小凹槽的结合。 6 确定形成的静电和水合贡献 DNA弯曲结构。