Leland Stanford Junior University

Laura E Edgington

Matthew S Bogyo

Martijn Verdoes

Fangfang Yin

Jiyoun Lee

Compounds which specifically inhibit legumain, also known as asparaginyl endopeptidase are provided. The compounds have an epoxide or N-Michael acceptor warhead, and have an asparagine side chain attached to a nitrogen atom in the backbone adjacent the warhead. The compounds also preferably comprise a proline residue adjacent the asparagine, and the compound may also contain a third residue and/or a label for cellular or in vivo imaging of active legumain.

Specific inhibitors and active site probes for legumain

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.

Growing community of inventors

Stanford, CA, United States of America

Laura E Edgington