Time-resolved fluorescence-based assay for the determination of alkaline phosphatase activity and application to the screening of its inhibitors

J Biomol Screen. 2008 Jan;13(1):9-16. doi: 10.1177/1087057107312031.

Abstract

A single-step end point method is presented for determination of the activity of the enzyme alkaline phosphatase (ALP) using the effect of enhancement of fluorescence of the easily accessible europium(III)-tetracycline 3:1 complex (Eu(3)TC). Its luminescence, peaking at 616 nm if excited at 405 nm, is enhanced by a factor of 2.5 in the presence of phosphate. Phenyl phosphate was used as a substrate that is enzymatically hydrolyzed to form phenol and phosphate. The latter coordinates to Eu(3)TC and enhances its luminescence intensity as a result of the displacement of water from the inner coordination sphere of the central metal. The assay is performed in a time-resolved (gated) mode, which is shown to yield larger signal changes than steady-state measurement of fluorescence. The limit of detection for ALP is 4 micromol L(-1). Based on this scheme, a model assay for theophylline as inhibitor for ALP was developed with a linear range from 14 to 68 micromol L(- 1) of theophylline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis*
  • Alkaline Phosphatase / antagonists & inhibitors*
  • Drug Evaluation, Preclinical / methods*
  • Enzyme Inhibitors / pharmacology
  • Europium
  • Fluorescent Dyes
  • Humans
  • In Vitro Techniques
  • Luminescence
  • Luminescent Measurements / methods
  • Organometallic Compounds
  • Phosphates
  • Spectrometry, Fluorescence / methods*
  • Tetracyclines
  • Theophylline / pharmacology

Substances

  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Organometallic Compounds
  • Phosphates
  • Tetracyclines
  • europium(III) tetracycline
  • Europium
  • Theophylline
  • Alkaline Phosphatase