Fiche publication
Date publication
avril 2016
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOURGUET Erika
,
Dr BRASSART-PASCO Sylvie
,
Pr SAPI Janos
,
Pr NABIEV Igor
,
Pr VILLENA Isabelle
Tous les auteurs :
Bourguet E, Brazhnik K, Sukhanova A, Moroy G, Brassart-Pasco S, Martin AP, Villena I, Bellon G, Sapi J, Nabiev I
Lien Pubmed
Résumé
The development of chemically designed matrix metalloprotease (MMP) inhibitors has advanced the understanding of the roles of MMPs in different diseases. Most MMP probes designed are fluorogenic substrates, often suffering from photo- and chemical instability and providing a fluorescence signal of moderate intensity, which is difficult to detect and analyze when dealing with crude biological samples. Here, an inhibitor that inhibits MMP-2 more selectively than Galardin has been synthesized and used for enzyme labeling and detection of the MMP-2 activity. A complete MMP-2 recognition complex consisting of a biotinylated MMP inhibitor tagged with the streptavidin-quantum dot (QD) conjugate has been prepared. This recognition complex, which is characterized by a narrow fluorescence emission spectrum, long fluorescence lifetime, and negligible photobleaching, has been demonstrated to specifically detect MMP-2 in in vitro sandwich-type biochemical assays with sensitivities orders of magnitude higher than those of the existing gold standards employing organic dyes. The approach developed can be used for specific in vitro visualization and testing of MMP-2 in cells and tissues with sensitivities significantly exceeding those of the best existing fluorogenic techniques.
Mots clés
Drug Design, Matrix Metalloproteinase 2, drug effects, Protease Inhibitors, chemistry, Quantum Dots
Référence
Bioconjug. Chem.. 2016 Apr;27(4):1067-81
