A gold coordination compound as a chemical probe to unravel aquaporin-7 function

Abstract

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological functions. Aquaporin-based modulators are predicted to have potential utility in the treatment of several diseases, as well as chemical tools to assess AQPs function in biological systems. We recently reported gold(III) compounds as human AQP3 inhibitors, with Auphen as the most potent of the series. In this work, we assessed the modulation of aquaporin-7 (AQP7) expressed in an adipocyte cell model and show that Auphen significantly inhibits mouse and human AQP7. By homology modeling and molecular docking it was possible to identify the thioether groups of methionine residues, in particular Met47, as likely candidates for binding to the gold(III) complex. Our data point to Auphen as a useful chemical tool to detect AQP7 function. It might constitute a basis to develop inhibitors with improved affinity towards different aquaglyceroporin isoforms.

Keywords: aquaporins; gold; inhibitors; membrane permeability; molecular modeling.