Fragment screening by SPR and advanced application to GPCRs

Claire A. Shepherd, Andrew L. Hopkins (Lead / Corresponding author), Iva Navratilova

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    Abstract

    Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). SPR biophysical GPCR assays using have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments.
    Original languageEnglish
    Pages (from-to)113-123
    Number of pages11
    JournalProgress in Biophysics and Molecular Biology
    Volume116
    Issue number2-3
    DOIs
    Publication statusPublished - Nov 2014

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