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) 项目支持。 太平洋大学的薛亮教授和同事 Andreas Franz、Jerry Tsai 和 Xiaoling Li 购买了一台等温滴定量热计 (ITC)。该技术用于确定溶液中相互作用的热力学参数。该仪器由封闭在绝热夹套中的两个单元组成，绝热夹套不允许所研究的系统与其周围环境之间发生热量传递，因此等温这个名称意味着相同的温度。热力学是化学物理学的一个分支，涉及热和温度及其与能量和功的关系。量热计用于研究配体与底物的结合和相互作用。在一项实验中，配体是一种小有机分子，底物是 DNA。测量相互作用的热力学。这种结合数据可能有助于研究可能的医学靶点。各种研究项目由本科生和高中生在暑假期间进行。社区学院德尔塔学院的学生也正在接受培训，使用这种在化学和生化领域有用的现代仪器。该仪器用于各个级别的研究和教育，特别是本科生。它被用来了解与 G-四链体 DNA 结合的 G4 配体，G-四链体 DNA 是由富含鸟嘌呤的序列在核酸中形成的二级结构。该仪器还用于验证旋钮-插座蛋白质堆积统计模型，该模型考虑了突起如何融入空隙。 蛋白质结合时聚糖的构象变化和水的释放正在研究中。 获得数据是为了了解小分子的结构，这些小分子可以稳定作为甲状腺激素载体的转运蛋白运甲状腺素蛋白。 该仪器还用于设计针对表皮生长因子受体 (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智力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

使用新霉素作为基于菲咯啉的 G 四链体配体和端粒酶抑制剂的结构化含氨基侧链基序

• DOI: 10.1111/cbdd.13741
• 发表时间: 2020-06-09
• 期刊: Chemical Biology & Drug Design
• 影响因子: 3
• 作者: M;eep Singh;eep;Siwen Wang;Hyun Joo;Zhihan Ye;K. Christison;Ryan M. Hekman;C. Vierra;L. Xue
• 通讯作者: L. Xue