First BRET-based screening assay performed in budding yeast leads to the discovery of CDK5/p25 interaction inhibitors. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Biotechnology Journal Année : 2011

First BRET-based screening assay performed in budding yeast leads to the discovery of CDK5/p25 interaction inhibitors.

Caroline Corbel
  • Fonction : Auteur
Qian Wang
Amel Hamdi
  • Fonction : Auteur
Bing Zhang
Olivier Lozach
Yoan Ferandin
  • Fonction : Auteur
Vincent B C Tan
  • Fonction : Auteur
Pierre Colas
  • Fonction : Auteur
Cyril Couturier
  • Fonction : Auteur
Stéphane Bach

Résumé

The protein kinase CDK5 (cyclin-dependent kinase 5) is activated through its association with a cyclin-like protein p35 or p39. In pathological conditions (such as Alzheimer's disease and various other neuropathies), truncation of p35 leads to the appearance of the p25 protein. The interaction of p25 with CDK5 up-regulates the kinase activity and modifies the substrate specificity. ATP-mimetic inhibitors of CDK5 have already been developed. However, the lack of selectivity of such inhibitors is often a matter of concern. An alternative approach can be used to identify highly specific inhibitors that disrupt protein interactions involving protein kinases. We have developed a bioluminescence resonance energy transfer (BRET)-based screening assay in yeast to discover protein-protein interaction inhibitors (P2I2). Here, we present the first use of BRET in yeast for the screening of small molecule libraries. This screening campaign led to the discovery of one molecule that prevents the interaction between CDK5 and p25, thus inhibiting the protein kinase activity. This molecule may give rise to high-specificity drug candidates.

Domaines

Chimie organique

Dates et versions

hal-00628746 , version 1 (04-10-2011)

Identifiants

Citer

Caroline Corbel, Qian Wang, Hadjira Bousserouel, Amel Hamdi, Bing Zhang, et al.. First BRET-based screening assay performed in budding yeast leads to the discovery of CDK5/p25 interaction inhibitors.. Biotechnology Journal, 2011, 6 (7), pp.860-70. ⟨10.1002/biot.201100138⟩. ⟨hal-00628746⟩
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