Fluorescence polarization assays in small molecule screening

Expert Opin Drug Discov. 2011 Jan;6(1):17-32. doi: 10.1517/17460441.2011.537322.

Abstract

Importance of the field: Fluorescence polarization (FP) is a homogeneous method that allows rapid and quantitative analysis of diverse molecular interactions and enzyme activities. This technique has been widely utilized in clinical and biomedical settings, including the diagnosis of certain diseases and monitoring therapeutic drug levels in body fluids. Recent developments in the field have been symbolized by the facile adoption of FP in high-throughput screening and small molecule drug discovery of an increasing range of target classes.

Areas covered in this review: The article provides a brief overview of the theoretical foundation of FP, followed by updates on recent advancements in its application for various drug target classes, including GPCRs, enzymes and protein-protein interactions. The strengths and weaknesses of this method, practical considerations in assay design, novel applications and future directions are also discussed.

What the reader will gain: The reader is informed of the most recent advancements and future directions of FP application to small molecule screening.

Take home message: In addition to its continued utilization in high-throughput screening, FP has expanded into new disease and target areas and has been marked by increased use of labeled small molecule ligands for receptor-binding studies.

Keywords: Competitive binding assay; drug discovery; enzyme assay; fluorescence anisotropy; fluorescence polarization; high throughput screening; ligand displacement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.