Instrument to quantify solution binding kinetics for drug discovery & development

用于药物发现的溶液结合动力学量化仪器

• 批准号: 7794532
• 负责人: JENNIFER A MAYNARD
• 金额: $ 17.13万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-20 至 2011-05-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7794532
• 关键词: Address; Area; Binding; Biological; Biological Phenomena; Carcinogenesis Mechanism; Communities; Complex; Core Facility; Data; Development; Disease; Dissociation; Equilibrium; Equipment; Funding; Health; Human; Institutes; Institution; Kinetics; Ligands; Measures; Minor; Molecular and Cellular Biology; Policies; Protein Binding; Proteins; Research; Solutions; Technology; Texas; Universities; austin; college; drug discovery; human disease; instrument; interest; novel therapeutics; public health relevance; rapid technique; small molecule; therapy development; water quality

DESCRIPTION (provided by applicant): We are requesting funds to purchase an instrument (KinExA) with the ability to sensitively and precisely measure binding kinetics from the millimolar to picomolar ranges and to quantify femptomolar concentrations of molecules of interest in complex solutions. These instruments will be used to identify, quantify and characterize small molecules and proteins that bind to biological targets of interest, which can then serve as starting points for drug discovery and development. There are no machines with the same capabilities available at the University of Texas at Austin or nearby campuses. UT does have one BIAcore 3000, able to measure binding kinetics to an immobilized ligand with less sensitivity, which is highly valued and receives very heavy use, such that it is practically unavailable to most users. The protein core facility owns a BIAcore 1000 which is available to most users, but has outlived its useful lifetime (produced circa 1990) and no longer produces reliable data. Regardless, these BIAcore machines do not possess several key desired capabilities: the ability to measure binding kinetics in solution, the ability to measure equilibrium dissociation constants as low as picomolar or as high as millimolar, or the ability to measure concentrations of molecules of interest when present at parts per trillion concentrations. The addition of a KinExA would therefore serve a unique purpose at UT Austin. The new equipment would be placed in the Institute for Molecular and Cellular Biology (ICMB) Protein Core Facility at UT and be available to the entire UT community. The ICMB has already established the space, staff, and recharge policies to maintain this equipment. The purchase of this instrument has broad support; the major and minor users listed in this proposal come from two institutions, three colleges and six departments, and their collective research interests address three NIH-funded themes: (1) drug discovery and development, (2) effects of water quality on human health and (3) basic mechanisms of carcinogenesis. Addition of these instruments will introduce radically new capabilities at the UT campus for drug discovery technologies and developing therapies in a variety of disease areas. PUBLIC HEALTH RELEVANCE: The KinExA instrument for which we are requesting funds represents a new, highly sensitive and rapid method for identifying and measuring the concentration of molecules with biological activity. These molecules can be used to interrogate basic biological phenomena or comprise new therapeutics for a wide variety of human diseases.

描述（由申请人提供）：我们要求资金购买一种仪器（Kinexa），能够敏感，精确地测量从毫米摩尔到皮摩尔范围的结合动力学，并量化复杂解决方案中利益分子的Fegemolor浓度。这些仪器将用于识别，量化和表征与感兴趣的生物学靶标结合的小分子和蛋白质，然后可以作为药物发现和发育的起点。德克萨斯大学奥斯汀分校或附近校园没有机器具有相同功能的机器。 UT确实有一个Biacore 3000，能够以较低的敏感性测量与固定配体的绑定动力学，这是高度重视并获得非常大量使用的，因此对于大多数用户来说，它实际上是无法使用的。蛋白质核心设施拥有Biacore 1000，大多数用户都可以使用，但已经超过了其有用的寿命（大约1990年生产），并且不再产生可靠的数据。无论如何，这些Biacore机器没有多种关键的期望功能：测量溶液中结合动力学的能力，测量平衡分离常数低如皮摩尔或高至毫米的能力，或者在以每三万亿浓度的零件为单位时测量利益分子浓度的能力。因此，Kinexa的添加将在UT Austin起独特的目的。新设备将放置在UT的分子和细胞生物学研究所（ICMB）蛋白质核心设施中，并可供整个UT社区使用。 ICMB已经建立了维护此设备的空间，员工和充电政策。购买该工具得到了广泛的支持；该提案中列出的主要和次要用户来自两个机构，三所大学和六个部门，其集体研究兴趣涉及三个由NIH资助的主题：（1）药物发现和开发，（2）水质对人类健康的影响以及（3）（3）癌变的基本机制。这些仪器的增加将在UT校园中引入新的新功能，用于药物发现技术，并在各种疾病地区开发疗法。 公共卫生相关性：我们要求资金的Kinexa仪器代表了一种新的，高度敏感和快速的方法，用于识别和测量具有生物活性的分子浓度。这些分子可用于询问基本的生物学现象或包括针对各种人类疾病的新疗法。

项目成果

Fine Epitope Mapping of Two Antibodies Neutralizing the Bordetella Adenylate Cyclase Toxin.

中和博德特氏菌腺苷酸环化酶毒素的两种抗体的精细表位作图。

• DOI: 10.1021/acs.biochem.6b01163
• 发表时间: 2017
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Wang,Xianzhe;Stapleton,JamesA;Klesmith,JustinR;Hewlett,ErikL;Whitehead,TimothyA;Maynard,JenniferA
• 通讯作者: Maynard,JenniferA