Scintillation proximity assay in lead discovery

Abstract

Background: Scintillation proximity assay (SPA) is a homogeneous scintillant bead-based platform for the measurement of biological processes and plays an important role in the identification of active chemical entities in drug discovery. Objective: The design and development of solid-phase SPA approaches are examined and compared with alternative non-radiometric fluorescence-based technologies. Methods: This review provides background on the principle of SPA and its application to biomolecular interactions from a variety of biological sources. Conclusion: The SPA approach is well suited to the demands of commercial high volume automation and assay miniaturization for target-based high-throughput screening campaigns on synthetic and natural product libraries as well as for benchtop characterization and confirmation studies. In the near future, innovations in the way SPA and fluorescence-based screening strategies are multiplexed will improve our comprehensive understanding of cellular system biology and dramatically advance the lead discovery process for the treatment of complex target-related disorders.

Keywords::

• ALPHAScreen
• BRET
• chemiluminescence
• DELFIA
• FLIPR
• fluorescence
• fluorescence polarization
• FRET
• [³⁵S]-GTPγS
• kinase
• radioimmunoassay
• receptor–ligand binding
• scintillation proximity
• SPA
• Transfluor

Notes