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Integrating surface plasmon resonance biosensor-based interaction kinetic analyses into the lead discovery and optimization process
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
2009 (English)In: Future Medicinal Chemistry, ISSN 1756-8919, Vol. 1, no 8, 1399-1414 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 1, no 8, 1399-1414 p.
National Category
Chemical Sciences
URN: urn:nbn:se:uu:diva-137614DOI: 10.4155/FMC.09.100ISI: 000276094100011OAI: oai:DiVA.org:uu-137614DiVA: diva2:378643
Available from: 2010-12-16 Created: 2010-12-15 Last updated: 2010-12-16Bibliographically approved

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