NON-PEPTIDIC QUENCHED FLUORESCENT IMAGING PROBES

摘要

Methods and materials for the imaging of cells and tissues containing active proteases such as cathepsin are disclosed. The present materials include activity based probes that bind to an enzyme and are subsequently cleaved. Cleavage results in covalent attachment of a fluorescent signal to a target protease due to removal of a quenching group which, when present on the probe causes altered or no fluorescence. The probes are non-peptidic, small molecule scaffolds linked to a reactive acyloxymethyl ketone group, a fluorophore and a quencher. The probes are cell permeable and may use, for example, a QSY21 (CAS 304014- 13-9) quencher and a cyanine dye. The probes form covalent bonds with the active site of cysteine cathepsins, proteases that are upregulated at the tumor boundaries with normal tissue and at sites of inflammation.