Arrêt de service lundi 11 juillet de 12h30 à 13h : tous les sites du CCSD (HAL, EpiSciences, SciencesConf, AureHAL) seront inaccessibles (branchement réseau à modifier)
Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules

Abstract : Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC50 around 58 μM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-grenoble-alpes.fr/hal-03039714
Contributeur : Frank Thomas Connectez-vous pour contacter le contributeur
Soumis le : jeudi 27 mai 2021 - 10:36:11
Dernière modification le : dimanche 26 juin 2022 - 03:08:48
Archivage à long terme le : : samedi 28 août 2021 - 18:29:53

Fichier

ArhabY_BessaaK_HoudaA_NoirielA...
Fichiers produits par l'(les) auteur(s)

Identifiants

Citation

yani Arhab, Karim Bessaa, Houda Abla, Meryem Aydin, Renaud Rahier, et al.. Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules. International Journal of Biological Macromolecules, Elsevier, 2021, 166, pp.1131-1140. ⟨10.1016/j.ijbiomac.2020.10.268⟩. ⟨hal-03039714⟩

Partager

Métriques

Consultations de la notice

99

Téléchargements de fichiers

86