title: Design, Synthesis, and Use of MMP-2 Inhibitor-Conjugated Quantum Dots in Functional Biochemical Assays.
abstract: 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.
authors.affiliation: Institut de Chimie Moléculaire de Reims, UMR 7312-CNRS, SFR Cap-Santé, UFR de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Bourguet
authors.affiliation: Laboratoire de Recherche en Nanosciences, LRN - EA4682, UFR de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.|Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) , 31 Kashirskoe shosse, 115409 Moscow, Russian Federation.
authors.forename: Kristina
authors.initials: K
authors.lastname: Brazhnik
authors.affiliation: Laboratoire de Recherche en Nanosciences, LRN - EA4682, UFR de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.|Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) , 31 Kashirskoe shosse, 115409 Moscow, Russian Federation.
authors.forename: Alyona
authors.initials: A
authors.lastname: Sukhanova
authors.affiliation: Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Université Paris Diderot, Sorbonne Paris Cité , 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Gautier
authors.initials: G
authors.lastname: Moroy
authors.affiliation: Laboratoire de Biochimie et de Biologie moléculaire, MEDyC, UMR CNRS/URCA 7369, SFR Cap-Santé, UFR de Médecine, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brassart-Pasco
authors.affiliation: Laboratoire de Biochimie et de Biologie moléculaire, MEDyC, UMR CNRS/URCA 7369, SFR Cap-Santé, UFR de Médecine, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.|Laboratoire de Parasitologie-Mycologie, EA3800, SFR Cap-Santé, UFR de Médecine, Université de Reims Champagne-Ardenne , 51 rue Cognacq-Jay, 51100 Reims, France.
authors.forename: Anne-Pascaline
authors.initials: AP
authors.lastname: Martin
authors.affiliation: Laboratoire de Parasitologie-Mycologie, EA3800, SFR Cap-Santé, UFR de Médecine, Université de Reims Champagne-Ardenne , 51 rue Cognacq-Jay, 51100 Reims, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Villena
authors.affiliation: Laboratoire de Biochimie et de Biologie moléculaire, MEDyC, UMR CNRS/URCA 7369, SFR Cap-Santé, UFR de Médecine, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Bellon
authors.affiliation: Institut de Chimie Moléculaire de Reims, UMR 7312-CNRS, SFR Cap-Santé, UFR de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.
authors.forename: Janos
authors.initials: J
authors.lastname: Sapi
authors.affiliation: Laboratoire de Recherche en Nanosciences, LRN - EA4682, UFR de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq Jay, 51100 Reims, France.|Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) , 31 Kashirskoe shosse, 115409 Moscow, Russian Federation.
authors.forename: Igor
authors.initials: I
authors.lastname: Nabiev
mesh_terms: D015195:Drug Design; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D045663:Quantum Dots
chemical_list: D011480:Protease Inhibitors; D020778:Matrix Metalloproteinase 2