An Integrated Approach to Diversity-Oriented Synthesis

面向多样性的综合综合方法

• 批准号: 7285266
• 负责人: STUART L SCHREIBER
• 金额: $ 183.95万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285266
• 关键词: Acetylene; Adopted; Alkaloids; Area; Azides; Biological; Biology; Bromine; Chemicals; Chemistry; Collaborations; Collection; Condition; Coupling; Cyclization; Descriptor; Development; Ensure; Lactams; Lead; Libraries; Link; Mediating; Medicine; Molecular; Numbers; Pathway interactions; Phase; Placement; Process; Quality Control; Range; Rate; Reaction; Reagent; Research; Research Personnel; Robot; Robotics; Screening procedure; Silicon; Skeletal system; Skeleton; Solid; Solutions; Standards of Weights and Measures; Technology; Transition Elements; Variant; Work; alkyl group; appendage; catalyst; cheminformatics; concept; cycloaddition; fundamental research; novel; programs; size; small molecule; stereochemistry; tool; virtual

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.

描述（由申请人提供）：面向多样性的合成（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。该中心将开展基础研究，以推进 DOS 可用的技术和途径，帮助充分发挥其潜力。我们将开发一个新平台（megabeads），该平台针对生物学家的筛选进行了优化；我们将使用 DOS 来发现新的催化剂，增加可用的 DOS 途径的范围；我们将开发几种新的库合成策略，探索目前人烟稀少的化学空间领域。两个核心将支持这些项目。文库合成、格式化和管理核心将致力于自动化反应开发，这是目前 DOS 中的限速步骤，并将通过以通用格式向现有 ICCB 筛选设施提供我们的文库，从而与生物筛选建立关键的联系。化学信息学核心将计算计划库的分子描述符，将它们与已知分子的参考集进行比较，并就如何最大限度地发挥给定库对化学空间探索的贡献向项目研究人员提供建议。