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Laboratory | Chemistry | Medical imaging | Cell and molecular imaging
Find research topics of the team "Metalloprotease functions"
Phosphinic peptidesZinc metalloproteases inhibitors can be obtained by functionalizing small peptides with an X group chelating the zinc ion in the active site of the enzyme (Fig. 1a) or by developing phosphinic inhibitors (Fig. 1b).
Transition state analoguesPhosphinic peptides by their resemblance to the substrate structure in transition state are considered to be transition state analogs.
Crystallographic structurePhosphinic inhibitor interacting with a zinc protease, astacin.
Examples of phosphinic inhibitors
MMP-12 selective inhibitor, the RXP470.1 By combinatorial chemistry approaches, our group has matched RXP470.1 compound (Fig. 5), the first potent and selective inhibitor of MMP-12, a zinc metalloprotease expressed by the macrophage in inflammatory conditions.
Crystal structure of RXP470.1 The high resolution of RXP470 crystallographic structure (1.15 Å, Fig. 6) interacting with the MMP-12 catalytic domain.
RXP470.1 and atherosclerosis model In a murine model of atherosclerosis, the treatment of mice by the RXP470.1 completely blocks plates growth and reduces their ability to break (Fig. 7).
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.