Manuel, Raoul and Lima, Michelle de Souza and Dilly, Sébastien and Daunay, Sylvain and Abbe, Patricia and Pramil, Elodie and Solier, Stéphanie and Guillaumond, Fabienne and Tubiana, Sarah-Simha and Escargueil, Alexandre and Pêgas Henriques, João Antonio and Ferrand, Nathalie and Erdelmeier, Irène and Boucher, Jean-Luc and Bertho, Gildas and Agranat, Israel and Rocchi, Stéphane and Sabbah, Michèle and Slama Schwok, Anny (2021) Distinction between 2′- and 3′-Phosphate Isomers of a Fluorescent NADPH Analogue Led to Strong Inhibition of Cancer Cells Migration. Antioxidants, 10 (5). p. 723. ISSN 2076-3921
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Abstract
Specific inhibition of NADPH oxidases (NOX) and NO-synthases (NOS), two enzymes associated with redox stress in tumor cells, has aroused great pharmacological interest. Here, we show how these enzymes distinguish between isomeric 2′- and 3′-phosphate derivatives, a difference used to improve the specificity of inhibition by isolated 2′- and 3′-phosphate isomers of our NADPH analogue NS1. Both isomers become fluorescent upon binding to their target proteins as observed by in vitro assay and in vivo imaging. The 2′-phosphate isomer of NS1 exerted more pronounced effects on NOS and NOX-dependent physiological responses than the 3′-phosphate isomer did. Docking and molecular dynamics simulations explain this specificity at the level of the NADPH site of NOX and NOS, where conserved arginine residues distinguished between the 2′-phosphate over the 3′-phosphate group, in favor of the 2′-phosphate.
Item Type: | Article |
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Subjects: | STM Library > Agricultural and Food Science |
Depositing User: | Managing Editor |
Date Deposited: | 11 Oct 2023 05:01 |
Last Modified: | 11 Oct 2023 05:01 |
URI: | http://open.journal4submit.com/id/eprint/2487 |