An Integrated Approach to Diversity-Oriented Synthesis

描述（由申请人提供）：多样性导向合成（DOS）有潜力使学术化学家和生物学家探索化学空间与生物活性之间的关系，从而导致生物学和医学的重大进步。该中心将进行基础研究，以推进DOS可用的技术和途径，帮助实现其全部潜力。我们将开发一个新的平台（megabead），优化生物学家的筛选；我们将利用DOS发现新的催化剂，增加DOS途径的可用范围；我们将开发几种新的图书馆合成策略，探索目前很少有人涉足的化学空间领域。两个核心将支持这些项目。库合成、格式和管理核心将致力于自动化反应开发，目前是DOS中的限速步骤，并将通过将我们的库以通用格式提供给现有的ICCB筛选设施，从而与生物筛选建立关键联系。化学信息学核心将计算计划文库的分子描述符，将它们与已知分子的参考集进行比较，并就如何最大化给定文库对化学空间探索的贡献向项目研究人员提供建议。

DESCRIPTION (provided by applicant): Diversity-oriented synthesis (DOS) has the potential to empower academic chemists and biologists to explore the relationship between chemistry space and biological activity, leading to major advances in biology and medicine. The Center will perform fundamental research to advance the technology and pathways available for DOS, to help realize its full potential. We will develop a new platform (megabeads) that is optimized for screening by biologists; we will use DOS to discover new catalysts, increasing the range of DOS pathways available; and we will develop several new strategies for library synthesis that explore areas of chemical space that are currently sparsely populated. Two Cores will support the Projects. The Library Synthesis, Formatting and Curation Core will work to automate reaction development, currently the rate-limiting step in DOS, and will make the crucial link to biological screening by providing our libraries to the existing ICCB screening facility in a common format. The Cheminformatics Core will compute molecular descriptors for planned libraries, compare them to a reference set of known molecules, and advise Project researchers on ways to maximize the contribution of a given library to the exploration of chemical space.