Doran Todd M, Dickson Paige, Ndungu John Maina, Ge Peng, Suponitsky-Kroyter Irena, An Hongchan, Kodadek Thomas
Department of Medicinal Chemistry and the Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, United States.
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, United States.
Methods Enzymol. 2019;622:91-127. doi: 10.1016/bs.mie.2019.02.005. Epub 2019 Mar 8.
The development of faster and less expensive methods to discover bioactive small molecules remains a high priority in chemical biology. This article discusses one alternative to traditional high-throughput screening: the synthesis and screening of one bead one compound (OBOC) libraries. Protocols are provided to create and screen libraries of peptoid displayed on TentaGel beads, which is a cheap and relatively straightforward process for the identification of selective protein ligands. However, peptoids bind to proteins with modest affinity in most cases. Therefore, we also describe protocols to create libraries of stiffer oligomers called PICCOs (peptoid-inspired, conformationally constrained oligomers) that have proven to be a superior source of high affinity ligands.
开发更快且成本更低的方法来发现生物活性小分子仍然是化学生物学中的一个高度优先事项。本文讨论了传统高通量筛选的一种替代方法：单珠单化合物（OBOC）文库的合成与筛选。文中提供了创建和筛选展示在TentaGel珠上的类肽文库的方案，这是一种用于鉴定选择性蛋白质配体的廉价且相对简单的过程。然而，在大多数情况下，类肽与蛋白质的结合亲和力适中。因此，我们还描述了创建称为PICCOs（类肽启发的、构象受限的寡聚物）的更刚性寡聚物文库的方案，这些寡聚物已被证明是高亲和力配体的优质来源。
