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- Title
Distinction between 2′- and 3′-Phosphate Isomers of a Fluorescent NADPH Analogue Led to Strong Inhibition of Cancer Cells Migration.
- Authors
Manuel, Raoul; Lima, Michelle de Souza; Dilly, Sébastien; Daunay, Sylvain; Abbe, Patricia; Pramil, Elodie; Solier, Stéphanie; Guillaumond, Fabienne; Tubiana, Sarah-Simha; Escargueil, Alexandre; Pêgas Henriques, João Antonio; Ferrand, Nathalie; Erdelmeier, Irène; Boucher, Jean-Luc; Bertho, Gildas; Agranat, Israel; Rocchi, Stéphane; Sabbah, Michèle; Slama Schwok, Anny; Ammendola, Rosario
- 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.
- Subjects
CANCER cell migration; ISOMERS; MOLECULAR dynamics; NICOTINAMIDE adenine dinucleotide phosphate; CARRIER proteins; CELL migration inhibition
- Publication
Antioxidants, 2021, Vol 10, Issue 5, p723
- ISSN
2076-3921
- Publication type
Article
- DOI
10.3390/antiox10050723