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.

该奖项得到了主要的研究工具（MRI）和化学研究工具（CRIF）计划的支持。 太平洋大学和同事安德烈亚斯·弗朗兹（Andreas Franz），杰里·赛（Jerry Tsai）和小李（li）的梁Xue教授已经收购了等温滴定热量表（ITC）。该技术用于确定溶液中相互作用的热力学参数。该仪器由两个封闭的绝热外套中的电池组成，该套件不允许在所研究的系统及其周围的系统之间传递热量，因此等温度为相同的温度。热力学是与热和温度有关的化学物理学分支及其与能量和工作的关系。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。测量相互作用的热力学。这种结合数据可能在研究可能的药物靶标方面很有用。夏季，本科生以及高中生进行了各种研究项目。来自社区学院三角洲学院的学生也正在接受培训，可以使用这种现代仪器，可用于化学和生化领域。该仪器用于各个级别的研究和教育，尤其是本科生。它被用来理解与G-四链体DNA结合的G4配体，该配体是通过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杆蛋白填料统计模型，该模型考虑了突起如何适合空隙。 正在研究血糖和水在蛋白质结合上的构象变化。 获得数据以理解稳定稳定甲状腺激素载体的转运蛋白经甲状腺素的小分子的结构。 该仪器还用于设计用于靶向表皮生长因子受体（EGFR）的肽的实验中。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，认为值得通过评估值得支持。

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