A Kinetic Comparison on the Inhibition of Adenosine Deaminase by Purine Drugs

Abstract

The effects of allopurinol, acyclovir and theophylline on the activity of adenosine deaminase (ADA) were studied in 50 mM sodium phosphate buffer pH 7.5 at 27°C, using a UV– Vis spectrophotometer. Adenosine deaminase is inhibited by these ligands, via different types of inhibition. Allopurinol, as a transition state analog of xanthine oxidase, and acyclovir competitively inhibit the catalytic activity of ADA. Inhibition constant values are 285 and 231 µM for allopurinol and acyclovir, respectively. Theophylline acts as a non-competitive inhibitor for ADA, which shows different affinity binding sites at various drug concentrations. There were two different types of inhibition constant, one of them due to a low concentration of the drug (Ki = 56 µM) and the other appearing at higher concentrations of theophylline (Ki = 201 µM). Thermodynamic parameters also show that ADA has two binding sites for theophylline.