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）：我们正在申请资金购买一台仪器（KinExA），该仪器能够灵敏、精确地测量从毫摩尔到皮摩尔范围的结合动力学，并定量复杂溶液中感兴趣分子的飞摩尔浓度。这些仪器将用于识别、量化和表征与感兴趣的生物靶标结合的小分子和蛋白质，然后可以作为药物发现和开发的起点。在德克萨斯大学奥斯汀分校或附近的校园里没有具有相同功能的机器。UT确实有一个BIAcore 3000，能够以较低的灵敏度测量与固定化配体的结合动力学，这是非常有价值的，并且得到了非常大量的使用，使得它实际上对大多数用户是不可用的。蛋白质核心设施拥有BIAcore 1000，可供大多数用户使用，但已超过其使用寿命（约1990年生产），不再产生可靠的数据。无论如何，这些BIAcore机器不具备几个关键的期望能力：测量溶液中结合动力学的能力，测量低至皮摩尔或高至毫摩尔的平衡解离常数的能力，或测量以万亿分之一浓度存在时的目标分子浓度的能力。因此，增加KinExA将在UT Austin发挥独特的作用。新设备将被放置在UT的分子和细胞生物学研究所（ICMB）蛋白质核心设施，并提供给整个UT社区。ICMB已经建立了空间、人员和充电政策来维护这些设备。该仪器的购买得到了广泛的支持;本提案中列出的主要和次要用户来自两个机构，三个学院和六个部门，他们的集体研究兴趣涉及三个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和（3）致癌的基本机制。这些仪器的增加将在UT校园引入全新的能力，用于药物发现技术和开发各种疾病领域的疗法。 公共卫生相关性：我们正在申请资金的KinExA仪器是一种新的、高度灵敏和快速的方法，用于识别和测量具有生物活性的分子的浓度。这些分子可用于询问基本的生物学现象或包括用于多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