Distinction between 2′- and 3′-Phosphate Isomers of a Fluorescent NADPH Analogue Led to Strong Inhibition of Cancer Cells Migration - Sorbonne Université Access content directly
Journal Articles Antioxidants Year : 2021

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

Raoul Manuel
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  • PersonId : 1101052
Michelle de Souza Lima
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Sébastien Dilly
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  • PersonId : 1067669
Sylvain Daunay
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  • PersonId : 1101053
Patricia Abbe
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  • PersonId : 1101054
Elodie Pramil
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  • PersonId : 1101055
Stéphanie Solier
Fabienne Guillaumond
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  • PersonId : 1101056
Sarah-Simha Tubiana
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Alexandre Escargueil
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João Antonio Pêgas Henriques
Nathalie Ferrand
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  • PersonId : 1101057
Irène Erdelmeier
Jean-Luc Boucher
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  • PersonId : 1101058
Gildas Bertho
Israel Agranat
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  • PersonId : 1101059
Stéphane Rocchi
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  • PersonId : 1101060
Michèle Sabbah
Anny Slama Schwok

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.
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hal-03990867 , version 1 (15-02-2023)

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Raoul Manuel, Michelle de Souza Lima, Sébastien Dilly, Sylvain Daunay, Patricia Abbe, et al.. Distinction between 2′- and 3′-Phosphate Isomers of a Fluorescent NADPH Analogue Led to Strong Inhibition of Cancer Cells Migration. Antioxidants , 2021, 10, ⟨10.3390/antiox10050723⟩. ⟨hal-03990867⟩
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