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. 2013 Jun 3;288(28):20568–20580. doi: 10.1074/jbc.M113.471508

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© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 2. — MP-3653/MP-3655 liposomal formulation structure and inhibitory activity. A, the structure and composition of MP-3653 and MP-3655. MP-3653 contains the inhibitory hydroxamate warhead (MP-3601) inserted into the lipid bilayer via a PEG(5000) linker. MP-3655 contains the inactive methyl ester warhead derivative (MP-3616) inserted into the lipid bilayer via a PEG(5000) linker. The DSPE-carboxyfluorescein moiety is inserted into the lipid bilayer via a PEG(2000) linker. Diethylene triamine pentaacetic acid (DTPA) is used for hydration of the liposomal samples. B, IC₅₀ values for MP-3653 against multiple MMPs. Left, the MMP activity was measured in the presence of increasing concentrations of MP-3653 (1 nm to 2 μm) using MCA-PLGL-Dpa-AR-NH₂ as a substrate. The MMP concentrations in the reactions were 10 nm. Right, a representative dose-response curve of MP-3653 against the catalytic domain of MT1-MMP. The inactive MP-3655 liposomal formulation (1 nm to 5 μm) was used as a control. RFU, relative fluorescence units.