Foster Andrew D, Ingram James D, Leitch Eilidh K, Lennard Katherine R, Osher Eliot L, Tavassoli Ali
Chemistry, University of Southampton, Southampton, UK.
Chemistry, University of Southampton, Southampton, UK Cancer Sciences, University of Southampton, Southampton, UK
J Biomol Screen. 2015 Jun;20(5):563-76. doi: 10.1177/1087057114566803. Epub 2015 Jan 13.
The identification of initial hits is a crucial stage in the drug discovery process. Although many projects adopt high-throughput screening of small-molecule libraries at this stage, there is significant potential for screening libraries of macromolecules created using chemical biology approaches. Not only can the production of the library be directly interfaced with a cell-based assay, but these libraries also require significantly fewer resources to generate and maintain. In this context, cyclic peptides are increasingly viewed as ideal scaffolds and have proven capability against challenging targets such as protein-protein interactions. Here we discuss a range of methods used for the creation of cyclic peptide libraries and detail examples of their successful implementation.
确定初始命中物是药物发现过程中的关键阶段。尽管许多项目在此阶段采用小分子文库的高通量筛选，但使用化学生物学方法创建的大分子文库的筛选具有巨大潜力。不仅文库的生产可以直接与基于细胞的检测相结合，而且生成和维护这些文库所需的资源也显著减少。在这种背景下，环肽越来越被视为理想的支架，并且已证明对诸如蛋白质-蛋白质相互作用等具有挑战性的靶点具有作用。在这里，我们讨论了一系列用于创建环肽文库的方法，并详细介绍了它们成功实施的实例。
