Design of Array-Type Compound Libraries that Combine Information from Natural Products and Synthetic Molecules
Design of Array-Type Compound Libraries that Combine Information from Natural Products and Synthetic Molecules
复制标题
结合天然产物和合成分子信息的阵列型化合物库的设计
DOI：
10.1007/s0089400060550
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
J. Bajorath
中科院分区：
文献类型：
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作者：
F. Stahura;L. Xue;J. Godden;J. Bajorath
提出了一种设计化合物文库的新方法，称为MetaFocus (Metabolite-Focused library)，该方法利用天然分子中编码的信息，并将天然存在的和合成的化合物结合起来。MF方法的一个重要目标是鉴定模拟天然分子性质的合成化合物，这些天然分子难以获得足够数量或难以合成。MetaFocus （MF）阵列中的化合物集中在具有良好治疗效果的天然分子上。相似性搜索和多样性设计技术用于生成化合物阵列，从选定的天然分子开始，添加天然或合成来源的相似分子，并使这些分子衍生的支架多样化。由于鉴定天然和合成来源的相似分子在我们的文库设计工作中起着重要作用，因此在一个由16个生物活性类别组成的新组装的测试数据库中，系统地评估了指纹型搜索工具的性能。MF数组被组织为易于扩展和搜索的数据结构，并作为药物发现应用的知识库。本文介绍了中频阵列的设计原理和结构，并给出了应用实例。
A new approach to the design of compound libraries, named MetaFocus (Metabolite-Focused library), is presented that exploits information encoded in natural molecules and combines naturally occurring and synthetic compounds. An important goal of the MF approach is the identification of synthetic compounds that mimic properties of natural molecules that are difficult to obtain in sufficient quantities or to synthesize. Compounds in MetaFocus (MF) arrays are focused on natural molecules with attractive therapeutic effects. Similarity search and diversity design techniques are employed to generate compound arrays that start from a selected natural molecule, add similar molecules, either from natural or synthetic sources, and diversify scaffolds derived from these molecules. Since the identification of similar molecules from natural and synthetic sources plays a significant role in our library design efforts, the performance of fingerprint-type search tools was systematically assessed in a newly assembled test database consisting of 16 biological activity classes. MF arrays are organized as an easily expandable and searchable data structure and serve as a knowledge base for drug discovery applications. Here we introduce the design principles and organization of MF arrays and present example applications.