New Synthetic Methods for Building Chip Based Libraries

这项工作将继续开发微电极阵列，作为探测小分子文库和生物受体之间相互作用的工具。微电极阵列的使用使得小分子和生物受体之间的相互作用可以被“实时”探测，而不需要像当前最先进的方法那样进行后续的清洗步骤。通过这种方式，可以收集关于被研究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，将探索新的现场选择性化学，以扩展阵列的一般合成能力。这项工作至关重要，因为它是一种可用于在阵列中构建微电极附近的分子的合成方法，它定义了可以在阵列上合成的分子类型，以及可以使用它们研究的生物学问题的性质。还将努力为微电极阵列开发与正在发现的合成方法兼容的新的聚合物涂层，设计和合成用于将分子连接到聚合物涂层的新连接物，以便能够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能力。通过这一奖项，有机和高分子化学计划支持圣路易斯华盛顿大学化学系的Kevin D.Moeller教授的研究。莫勒教授的研究涉及开发合成有机分子并探索其生物活性的电化学方法。拟议工作的长期影响将大大增强我们绘制治疗靶点的三维结合基序的能力，并更有效地指导设计新的配体和潜在的治疗剂。在这项工作中，微电极阵列将被开发并用作跟踪分子与其目标受体之间发生相互作用的工具。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。

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.