Assay Method Information

Assay Name:  IC50 Determination
Description:  Experiments to determine IC50 values against β5i and β5c for compounds were carried out in 96-well plates. In brief, 1 μL of compound in a 3× series dilution in DMSO at concentration ranging from 100 μM-0.0017 μM were spotted to the bottom of a black 96-well plate with solid bottom. 100 μL of reaction buffer (20 mM HEPES, 0.5 mM EDTA, pH7.5, 0.1% BSA) containing enzyme (final concentration was 0.2 nM for c-20S, and 0.4 nM for i-20S) and substrate (25 μM for suc-LLVY-AMC for β5c and 15 μM for Ac-ANW-AMC) were dispensed into each well, and the plate was then spun at 1000× rpm for 1 minute and then shaked on a shaker for 1 minute. Time course of the hydrolysis of each well was followed by recording the fluorescence of product AMC (Ex 360 nm and Em 460 nm) on a SpectraMax M5 plate reader for 1.5-2 hours. Initial reaction velocity of each well was fit to a dose-dependent inhibition equation using PRISM to determine the IC50. IC50s were determined only for β5i and β5c (Table 3). SDS was used as activator for both enzymes at concentration 0.0200.
Affinity data for this assay
 

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