Fig. 4: Kinetic of Caspase-2 vs. Caspase-3 inhibitions by TRP601, Δ2Me-TRP601, and LJ2.
From: Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics
a, c Progress curves of Ac-VDVAD-AMC hydrolysis catalyzed by caspase-2 in the presence of various concentrations of LJ2 (a) and Δ2Me-TRP601 (c), as indicated. The data were obtained under the conditions described in the Materials and methods section (25 μM substrate and 0.2 nM Caspase-2) and analyzed according to Eqs. (2–5). b Values of kobs obtained from panel “a” plotted versus LJ2 concentrations. d Values of kobs obtained from panel “c” plotted versus Δ2Me-TRP601 concentrations. e, g Progress curves of Ac-DEVD-AMC hydrolysis catalyzed by caspase-3 in the presence of various concentrations of LJ2 (e) and Δ2Me-TRP601 (g), as indicated. The data were obtained under the conditions described in the Materials and methods section (10 μM substrate and 0.1 nM Caspase-3) and analyzed according to Eq. (2). f Values of kobs obtained from panel “e” plotted versus LJ2 concentrations. h Values of kobs obtained from panel “g” plotted vs. Δ2Me-TRP601 concentrations. i The plots in b, d, f, and h was fit according to Eq. (3) to generate KI and kinact (k3) respective values. Indicated Ki and k3 value of each inhibitor on Caspase-2 and Caspase-3 are mean values from five independent experiments (SE < 0.07). Koff rates (k3/Ki) and Casp3/Casp2 selectivity ratio (Koff rates Casp3/Koff rates Casp2) are also indicated.
