SOLID PHASE INTERATIVE BIOCATALYSIS FOR DRUG DISCOVERY

描述(改编自申请)：新药的标识 候选和随后合成的大量新的衍生品是 药物开发中的关键步骤，但既耗时又昂贵 具有最佳生物活性。这一分两个阶段的计划的目标是 固相组合生物催化作为一种新型生物催化技术的研究进展 用于快速生成分子库的通用方法 生物活性化合物，如抗癌剂和其他类型的 毒品，是可以获得的。第一阶段的具体目标是： 1.将抗癌化合物阿霉素固定在固体载体上并实施 阿霉素衍生物从载体上的酶释放策略； 2.通过以下方法鉴定溶液中对阿霉素具有反应性的酶 高通量筛网的应用； 3.将现有的蛋白酶在有机溶剂中的增溶方法应用于 用于修饰附着在固体上的底物的不同酶类 支架； 4.用溶解于两种水中的酶对固载阿霉素进行修饰 和有机媒体。 这项研究代表了Albany的一个部门EnzyMed的合作 爱荷华州爱荷华市的分子研究公司和爱荷华州大学的研究人员 加州大学伯克利分校和伦斯勒理工学院。第一阶段的重点是 开发固相生物催化组合化学的基本工具。在……里面 第二阶段申请者将对这些工具进行扩展以生成和筛选 具有抗癌活性的天然产物衍生物库。 建议的商业应用： 提出的固相组合生物催化的商业应用是 作为一种生产药物和其他高价值化合物的新方法。 新的阿霉素衍生物也可能在抗癌方面有商业应用 药物和作为治疗其他疾病的药物。

DESCRIPTION (Adapted from the application): The identification of new drug candidates and subsequent synthesis of large numbers of new derivatives are crucial, yet time-consuming and expensive, steps in the development of drugs with optimal biological activity. The objective of this two-phase program is the development of solid-phase combinatorial biocatalysis as a new and versatile method for rapidly generating libraries of molecules from which biologically active compounds, such as anticancer agents and other types of drugs, can be obtained. The specific aims of Phase I are: 1. Attach the anticancer compound doxorubicin to a solid support and implement strategies for enzymatic release of doxorubicin derivatives from the support; 2. Identify enzymes with reactivity against doxorubicin in solution through application of high-throughput screens; 3. Apply existing methods of protease solubilization in organic solvents to different enzyme classes for modification of substrates attached to solid supports; 4. Modify solid-supported doxorubicin using enzymes dissolved in both aqueous and organic media. This research represents a collaboration between EnzyMed, a division of Albany Molecular Research, Inc., in Iowa City, Iowa, and researchers at the University of California Berkeley, and Rensselaer Polytechnic Institute. The focus of Phase I is to develop the basic tools of solid-phase biocatalytic combinatorial chemistry. In Phase II the applicant will expand upon these tools to generate and screen libraries of natural product derivatives for anticancer activity. PROPOSED COMMERCIAL APPLICATION: The proposed commercial application of solid-phase combinatorial biocatalysis is as a new method for generating pharmaceuticals and other high-value compounds. New doxorubicin derivatives may also have commercial applications as anticancer drugs and as therapeutics against other diseases.