New Synthetic Methods for Building Chip Based Libraries

构建基于芯片的文库的新合成方法

• 批准号: 0909723
• 负责人: Kevin Moeller
• 金额: $ 45.5万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0909723&HistoricalAwards=false
• 关键词: New; Synthetic; Methods; Building; Chip

This work will continue the development of microelectrode arrays as tools for probing interactions between small molecule libraries and biological receptors. The use of the microelectrode arrays allows for interactions between small molecules and biological receptors to be probed in "real-time" without the need for the subsequent washing steps typical of current state-of-the-art methods. In this way, more accurate information can be gathered about the three dimensional binding preferences of the receptor being studied. During the upcoming budget period, new site-selective chemistry that extends the general synthetic capabilities of the arrays will be explored. This work is essential because it is the synthetic methodology available for building molecules proximal to the microelectrodes in an array that defines both types of molecules that can be synthesized on the arrays and the nature of the biological problems that can be studied using them. Efforts will also be made to develop new polymer coatings for the microelectrode arrays that are compatible with the synthetic methods being discovered, to design and synthesize new linkers for attaching molecules to the polymer coatings so that the members of a molecular library on the arrays can be readily characterized, and to optimize the signaling capabilities of microelectrode arrays.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Kevin D. Moeller of the Department of Chemistry at Washington University in St. Louis. Professor Moeller's research involves the development of electrochemical methods for synthesizing organic molecules and probing their biological activity. The long-range impact of the proposed work will be to greatly enhance our ability to map the three-dimensional binding motifs of therapeutic targets and more effectively guide the design of new ligands and potential therapeutic agents for them. In this effort, microelectrode arrays will be developed and employed as tools for following the interactions between molecules and their targeted receptors as they happen. Successful accomplishment of this project will have a positive impact on the pharmaceutical and biotechnology industries.

这项工作将继续发展微电极阵列作为探测小分子库和生物受体之间相互作用的工具。微电极阵列的使用允许“实时”探测小分子和生物受体之间的相互作用，而不需要当前最先进方法的典型的后续洗涤步骤。通过这种方式，可以收集关于所研究的受体的三维结合偏好的更准确的信息。在即将到来的预算期间，将探索新的选址化学，扩大阵列的一般合成能力。这项工作是必不可少的，因为它是合成方法，可用于构建分子接近微电极的阵列，定义了两种类型的分子，可以在阵列上合成和生物学问题的性质，可以使用它们进行研究。此外，还将致力于开发与正在发现的合成方法兼容的用于微电极阵列的新聚合物涂层，设计和合成用于将分子连接到聚合物涂层的新连接体，以便可以容易地表征阵列上的分子库成员，并优化微电极阵列的信号传导能力。有机和高分子化学计划是支持教授凯文D。位于圣路易斯的华盛顿大学化学系的Moeller说。 Moeller教授的研究涉及合成有机分子和探测其生物活性的电化学方法的发展。拟议工作的长期影响将大大提高我们绘制治疗靶点的三维结合基序的能力，并更有效地指导新配体和潜在治疗剂的设计。在这项工作中，微电极阵列将被开发和使用，作为跟踪分子与其靶向受体之间相互作用的工具。 该项目的成功完成将对制药和生物技术行业产生积极影响。