NOVEL SOLID PHASE SUPPORTS FOR COMBINATORIAL CHEMISTRY

描述：（主要研究者）本提案的目的是 多用途聚合物载体的设计、制备和对比试验 这将为更快、更高效、更化学地 不同的或更大规模的固相合成的组合文库， 生物活性化合物。 主要目标包括功能性有机 具有优化的形状、尺寸、容量、交联密度 孔隙率和化学性质。 这些材料将被设计为补充 目前可用的支持，同时提供大幅改善 在制备组合文库中的性能， 其增加的多功能性、容量、批次间再现性，以及 体化学和表面化学的适当组合。 具体地说， 我们计划探索凝胶和大孔珠以及整体支持物， 和形状的物体。 我们对球形尺寸单分散载体的方法 将涉及两种市售单体和特种单体。 的 较大的均匀尺寸的珠粒（200微米至1毫米）的制备将 涉及开发全新的制备程序， 按比例放大。 使用大型整体支撑和成型物体将 提供新的机会，如简单的跟踪， 该自动化设备，高负荷能力，并在一个流通的工作 政权 开发具有新化学成分的支架是我们最重要的 重要目标。 除了直接使用非传统的 单体，如甲基丙烯酸酯和取代的苯乙烯， 修饰反应将导致支持物允许独特的标记， 金属离子 最初的光敏连接剂将被开发用于广泛的应用。 光谱支持。 新的三维多功能连接体将 提高容量并促进孔空间内的反应。 聚合物负载的助剂如固相试剂，清除剂， 简化液相的催化剂、猝灭剂和共溶剂 组合合成是该提议的另一个目标。 总体看 提供各种格式的优化支持将有助于 发现新的线索，加速新药的转移， 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.