Department of Biochemistry and Organic Chemistry, Uppsala University, Sweden.
Future Med Chem. 2009 Nov;1(8):1399-414. doi: 10.4155/fmc.09.100.
Surface plasmon resonance biosensor technology has come of age and become an important tool for drug discovery. It is a label-free biophysical technique for the kinetic analysis of molecular interactions that provides exceptionally information-rich data. Recent improvements in sensitivity, experimental design, data analysis and sample throughput makes it suitable for use throughout the drug-discovery process. This article outlines the use of SPR biosensor technology for small-molecule drug discovery and exemplifies how it complements other techniques. The technology is especially valuable for fragment-based lead discovery since it has the required sensitivity and throughput for screening of fragment libraries. Hits can be identified with respect to multiple criteria, defined by the experimental design used for screening. Expansion of hits and subsequent characterization and optimization of leads can be performed with a variety of experiments exploiting the kinetic resolution of the technology. Leads identified by this strategy can therefore be extensively characterized with respect to their interactions, with their target as well as with nontarget proteins. Although it may take some time for the methods to become well established, and for the research community to reach proficiency and fully embrace the information-rich data that can be obtained, it can be predicted that this technology will be widely used for drug discovery within the near future. It is expected that the technology will be particularly important for fragment-based strategies and integrated with other experimental technologies as well as with computational methods.
表面等离子体共振生物传感器技术已经成熟，成为药物发现的重要工具。它是一种无标记的生物物理技术，用于分子相互作用的动力学分析，可以提供非常丰富的信息。近年来，该技术在灵敏度、实验设计、数据分析和样品通量方面的改进使其适用于药物发现过程的各个阶段。本文概述了表面等离子体共振生物传感器技术在小分子药物发现中的应用，并举例说明了它如何与其他技术相辅相成。该技术特别适用于基于片段的先导化合物发现，因为它具有筛选片段文库所需的灵敏度和通量。可以根据用于筛选的实验设计定义多个标准来识别命中化合物。可以使用各种实验来扩展命中化合物，并随后对先导化合物进行表征和优化，从而利用该技术的动力学分辨率。因此，可以根据其与靶蛋白和非靶蛋白的相互作用，对通过该策略鉴定的先导化合物进行广泛的表征。尽管这些方法需要一些时间才能得到很好的确立，并且研究界需要达到熟练程度并充分利用可以获得的丰富信息，但可以预测，该技术将在不久的将来被广泛用于药物发现。预计该技术将特别重要，特别是对于基于片段的策略，并与其他实验技术以及计算方法相结合。
