title: 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.
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa (Portugal); Dept. Bioquimica e Biologia Humana, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa (Portugal).
authors.forename: Ana
authors.initials: A
authors.lastname: Madeira
authors.forename: Andreia
authors.initials: A
authors.lastname: de Almeida
authors.forename: Chris
authors.initials: C
authors.lastname: de Graaf
authors.forename: Marta
authors.initials: M
authors.lastname: Camps
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.forename: Teresa F
authors.initials: TF
authors.lastname: Moura
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Graça
authors.initials: G
authors.lastname: Soveral
mesh_terms: D016475:3T3 Cells; D000818:Animals; D020346:Aquaporins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C114141:AQP7 protein, human; C491927:Aqp7 protein, mouse; D020346:Aquaporins; D050607:Organogold Compounds
keywords: aquaporins; gold; inhibitors; membrane permeability; molecular modeling