MRI: Acquisition of An Isothermal Titration Calorimeter for Studying Ligand-Macromolecule Interactions

MRI：获取等温滴定量热计用于研究配体-大分子相互作用

• 批准号: 1828179
• 负责人: Liang Xue
• 金额: $ 14.03万
• 依托单位: University of the Pacific
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1828179&HistoricalAwards=false
• 关键词: MRI; Acquisition; Isothermal; Titration; Calorimeter

This award is supported by the Major Research Instrumentation (MRI) and the Chemistry Research Instrumentation (CRIF) Programs. Professor Liang Xue from the University of the Pacific and colleagues Andreas Franz, Jerry Tsai and Xiaoling Li have acquired an isothermal titration calorimeter (ITC). This technique is used to determine the thermodynamic parameters of interactions in solution. The instrument consists of two cells enclosed in an adiabatic jacket that does not allow transfer of heat between the system being studied and its surrounding, thus the name isothermal meaning same temperature. Thermodynamics is the branch of chemical physics concerned with heat and temperature and their relation to energy and work. The calorimeter is used to study the binding and interaction of a ligand with a substrate. In one experiment the ligand is a small organic molecule and the substrate is DNA. The thermodynamics of the interaction is measured. Such binding data may be useful in investigating possible medicinal targets. The various research projects are undertaken by undergraduate students as well as high school students during the summer. Students from Delta College, a community college, are also being trained to use this modern instrumentation useful in the chemical and biochemical fields. The instrument is used in research and education at all levels, particularly by undergraduate students. It is being used to understand G4 ligands binding to G-quadruplex DNA which are secondary structures formed in nucleic acids by sequences rich in guanine. The instrument is also employed to validate the knob-socket protein packing statistical model which considers how protuberances fit into voids. The conformational changes of glycan and water liberation upon protein binding is being studied. Data are obtained to understand the structures of small molecules that stabilize the transport protein transthyretin that serves as carrier of the thyroid hormone. The instrument is also used in experiments designing peptides for targeting the epidermal growth factor receptor (EGFR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项由主要研究仪器（MRI）和化学研究仪器（CRIF）计划支持。 来自太平洋大学的Liang Xue教授及其同事Andreas Franz，Jerry Tsai和Xiaoling Li获得了一台等温滴定量热仪（ITC）。该技术用于确定溶液中相互作用的热力学参数。该仪器由两个封闭在绝热夹套中的单元组成，绝热夹套不允许被研究的系统与其周围环境之间的热传递，因此名称等温意味着相同的温度。热力学是化学物理学的一个分支，主要研究热量和温度以及它们与能量和功的关系。量热计用于研究配体与底物的结合和相互作用。在一个实验中，配体是一个小的有机分子，底物是DNA。测量了相互作用的热力学。这种结合数据可能有助于研究可能的药物靶点。各种研究项目由本科生和高中生在夏季进行。来自社区学院德尔塔学院的学生也正在接受培训，以使用这种在化学和生物化学领域有用的现代仪器。该仪器用于各级研究和教育，特别是本科生。它被用来理解G4配体结合G-四链体DNA，这是由富含鸟嘌呤的序列在核酸中形成的二级结构。该仪器也被用来验证旋钮插座蛋白包装的统计模型，考虑如何突起适合到空隙。 蛋白质结合后聚糖的构象变化和水的释放正在研究中。 获得的数据，以了解小分子的结构，稳定的运输蛋白甲状腺素运载蛋白，作为载体的甲状腺激素。 该仪器还用于设计靶向表皮生长因子受体（EGFR）的肽的实验。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Use of neomycin as a structured amino‐containing side chain motif for phenanthroline‐based G‐quadruplex ligands and telomerase inhibitors

• DOI: 10.1111/cbdd.13741
• 发表时间: 2020-06
• 期刊: Chemical Biology & Drug Design
• 影响因子: 3
• 作者: Mandeep Singh;Siwen Wang;Hyun Joo;Zhihan Ye;K. Christison;Ryan M. Hekman;C. Vierra;L. Xue