NOVEL SOLID PHASE SUPPORTS FOR COMBINATORIAL CHEMISTRY

描述：(首席调查员)这项提议的目的是 多功能聚合物载体的设计、制备及对比试验 这将提供新的机会，以实现更快、更高效和更化学的 不同的或更大规模的组合文库的固相合成 具有生物活性的化合物。主要目标包括功能有机 具有优化的形状、尺寸、容量、交联度、 孔洞和化学物质。这些材料将被设计成补充 目前可用的支持，同时提供显著改进的 在组合文库的制备中的表现，作为结果 它们的多功能性、容量、批次之间的重复性以及 体相和表面相结合的合适组合。具体来说， 我们计划探索凝胶和大孔微珠以及整体载体。 和有形状的物体。我们对球形尺寸单分散支撑体的研究 将涉及商业上可用的BOT和特种单体。这个 制备更大的均匀尺寸的珠子(200微米到1毫米)将 参与开发全新的准备程序，使之更容易 放大。使用大型整体支撑件和成形物体将 提供新的机会，例如简单的跟踪、轻松处理 自动化设备，高承载能力，工作在流水线上 政权。开发具有新化学成分的载体是我们最重要的工作之一 重要的目标。除了直接使用非传统的 单体，如甲基丙烯酸酯和取代苯乙烯，具有空间靶向性 修改反应将产生支持，从而允许使用 金属离子。原创的光活性连接剂也将被广泛开发 支架的光谱。新的三维多功能链接器将 增强能力，促进毛孔空间内的反应。 聚合物支持的助剂，如固相试剂，清除剂， 简化液相的催化剂、猝灭剂和助溶剂 组合合成是这一提议的另一个目标。总体而言， 各种格式的优化支持的可用性将有助于 发现新的线索，加快新药向 测试和制造。

DESCRIPTION: (Principal Investigator's) The aims of this proposal are the design, preparation and comparative testing of versatile polymeric supports that will offer new opportunities for faster, more efficient and chemically diverse, or larger scale solid phase syntheses of combinatorial libraries of biologically active compounds. The major targets include functional organic polymers with optimized shapes, sizes, capacity, crosslinking densities, porosities, and chemistries. These materials will be designed to complement th currently available supports while providing substantially improved performanc in the preparation of combinatorial libraries as a result of their increased versatility, capacity, batch-to-batch reproducibility, and the suitable combination of both bulk and surface chemistry. Specifically, we plan to explore gel and macroporous beads as well as monolithic supports and shaped objects. Our approach to spherical size monodisperse supports will involve bot commercially available and specialty monomers. The preparation of larger uniformly sized beads (200 microm to 1 mm) will involve the development of totally new preparative procedures for easier scale-up. The use of large monolithic supports and shaped objects will provide new opportunities such as simple tracking, ease of handling within the automated devices, high loading capacity, and work in a flow-through regime. The development of supports with new chemistries is one of our most important objectives. In addition to the direct use of non-traditional monomers, such as methacrylates and substituted styrenes, spatially targeted modification reactions will result in supports allowing unique tagging with metal ions. Original photoactive linkers will als be developed for a broad spectrum of supports. New 3-dimensional multifunctional linkers will enhance capacity and facilitate reactions within the space of the pores. Polymer-supported auxiliaries such as solid-phase reagents, scavengers, catalysts, quenchers, and cosolvents that simplify liquid-phase combinatorial syntheses are another target of this proposal. Overall, the availability of optimized supports in a variety of formats will contribute to the discovery of new leads and accelerate the transfer of new drugs to testing and manufacturing.