Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules - Groupe Métalloprotéines / Metalloproteins Group (IBS-METALLO) Access content directly
Journal Articles International Journal of Biological Macromolecules Year : 2021

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.
Fichier principal
Vignette du fichier
ArhabY_BessaaK_HoudaA_NoirielA_2021.pdf (1.83 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03039714 , version 1 (27-05-2021)

Identifiers

Cite

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, 2021, 166, pp.1131-1140. ⟨10.1016/j.ijbiomac.2020.10.268⟩. ⟨hal-03039714⟩
125 View
126 Download

Altmetric

Share

Gmail Facebook X LinkedIn More