Distinction between 2′- and 3′-Phosphate Isomers of a Fluorescent NADPH Analogue Led to Strong Inhibition of Cancer Cells Migration

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
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

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