Fragment Screening by Surface Plasmon Resonance

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

    Research output: Contribution to journalArticlepeer-review

    105 Citations (Scopus)

    Abstract

    Fragment-based drug discovery is a validated approach for the discovery of drug candidates However, the weak affinity of fragment compounds requires highly sensitive biophysical techniques, such as nuclear magnetic resonance (NMR) or X-ray crystallography, to Identify hits. Thus the advantages of screening small fragment libraries are partly offset by the high cost of biophysical analyses Here we present a method for biosensor-based fragment screening using surface plasmon resonance (SFR) In order to reduce the false positive detection rate we present a novel method of data analysis that incorporates multiple referencing with ligand efficiency. By implementing all necessary steps for assay design. data analysis and interpretation, SPR-based fragment screening has potential to eliminate all nonspecific (false positive) binders Therefore, given the advantages of low protein consumption. rapid assay development and kinetic and thermodynamic validation of hits, SPR can be considered as a primary screening technology for fragment-based drug discovery

    Original languageEnglish
    Pages (from-to)44-48
    Number of pages5
    JournalACS Medicinal Chemistry Letters
    Volume1
    Issue number1
    DOIs
    Publication statusPublished - Apr 2010

    Keywords

    • Fragment screening
    • surface plasmon resonance
    • ligand efficiency
    • BIACORE TECHNOLOGY
    • DISCOVERY
    • DRUGGABILITY
    • INHIBITORS
    • BINDING

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