Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration

Raoul Manuel; Michelle de Souza Lima; Sébastien Dilly; Sylvain Daunay; Patricia Abbe; Elodie Pramil; Stéphanie Solier; Fabienne Guillaumond; Sarah Simha Tubiana; Alexandre Escargueil; João Antonio Pêgas Henriques; Nathalie Ferrand; Irène Erdelmeier; Jean Luc Boucher; Gildas Bertho; Israel Agranat; Stéphane Rocchi; Michèle Sabbah; Anny Slama Schwok

doi:10.3390/antiox10050723

Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration

Raoul Manuel, Michelle de Souza Lima, Sébastien Dilly, Sylvain Daunay, Patricia Abbe, Elodie Pramil, Stéphanie Solier, Fabienne Guillaumond, Sarah Simha Tubiana, Alexandre Escargueil, João Antonio Pêgas Henriques, Nathalie Ferrand, Irène Erdelmeier, Jean Luc Boucher, Gildas Bertho, Israel Agranat, Stéphane Rocchi, Michèle Sabbah, Anny Slama Schwok^*

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 differ-ence 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 pro-nounced 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.

Original language	English
Article number	723
Journal	Antioxidants
Volume	10
Issue number	5
DOIs	https://doi.org/10.3390/antiox10050723
State	Published - May 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Cancer cell migration
Fluorescence
In vivo imaging
Molecular modeling
NADPH oxidases
NO-syn-thases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/antiox10050723

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Manuel, R., Lima, M. D. S., Dilly, S., Daunay, S., Abbe, P., Pramil, E., Solier, S., Guillaumond, F., Tubiana, S. S., Escargueil, A., Henriques, J. A. P., Ferrand, N., Erdelmeier, I., Boucher, J. L., Bertho, G., Agranat, I., Rocchi, S., Sabbah, M., & Schwok, A. S. (2021). Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration. Antioxidants, 10(5), Article 723. https://doi.org/10.3390/antiox10050723

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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",

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 differ-ence 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 pro-nounced 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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author = "Raoul Manuel and Lima, {Michelle de Souza} and S{\'e}bastien Dilly and Sylvain Daunay and Patricia Abbe and Elodie Pramil and St{\'e}phanie Solier and Fabienne Guillaumond and Tubiana, {Sarah Simha} and Alexandre Escargueil and Henriques, {Jo{\~a}o Antonio P{\^e}gas} and Nathalie Ferrand and Ir{\`e}ne Erdelmeier and Boucher, {Jean Luc} and Gildas Bertho and Israel Agranat and St{\'e}phane Rocchi and Mich{\`e}le Sabbah and Schwok, {Anny Slama}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = may,

doi = "10.3390/antiox10050723",

language = "אנגלית",

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Manuel, R, Lima, MDS, Dilly, S, Daunay, S, Abbe, P, Pramil, E, Solier, S, Guillaumond, F, Tubiana, SS, Escargueil, A, Henriques, JAP, Ferrand, N, Erdelmeier, I, Boucher, JL, Bertho, G, Agranat, I, Rocchi, S, Sabbah, M & Schwok, AS 2021, 'Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration', Antioxidants, vol. 10, no. 5, 723. https://doi.org/10.3390/antiox10050723

TY - JOUR

T1 - Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration

AU - Manuel, Raoul

AU - Lima, Michelle de Souza

AU - Dilly, Sébastien

AU - Daunay, Sylvain

AU - Abbe, Patricia

AU - Pramil, Elodie

AU - Solier, Stéphanie

AU - Guillaumond, Fabienne

AU - Tubiana, Sarah Simha

AU - Escargueil, Alexandre

AU - Henriques, João Antonio Pêgas

AU - Ferrand, Nathalie

AU - Erdelmeier, Irène

AU - Boucher, Jean Luc

AU - Bertho, Gildas

AU - Agranat, Israel

AU - Rocchi, Stéphane

AU - Sabbah, Michèle

AU - Schwok, Anny Slama

PY - 2021/5

Y1 - 2021/5

N2 - 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 differ-ence 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 pro-nounced 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.

AB - 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 differ-ence 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 pro-nounced 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.

KW - Cancer cell migration

KW - Fluorescence

KW - In vivo imaging

KW - Molecular modeling

KW - NADPH oxidases

KW - NO-syn-thases

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AN - SCOPUS:85105128463

SN - 2076-3921

VL - 10

JO - Antioxidants

JF - Antioxidants

IS - 5

M1 - 723

ER -

Distinction between 2′-and 3′-phosphate isomers of a fluorescent nadph analogue led to strong inhibition of cancer cells migration

Abstract

Bibliographical note

Keywords

UN SDGs

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