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AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsJianghong Rao, Deju Ye, Adam Shuhendler, Frederick Te-Ning Chin, Jongho Jeon, Bin Shen
Estimating the term…
Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.
An activatable probe comprising a detachable capping moiety conjugated to a self-cyclizing molecule comprising a cysteine moiety, a 2-cyano-6-hydroxyquinoline moiety, and an amino luciferin scaffold, and a detectable imaging moiety.
A nano-aggregation probe, wherein said nano-aggregation probe is an aggregate of an activated probe, wherein said activated probe comprises a self-cyclized molecule having the formula V:
A method of forming a nano-aggregation probe comprising delivering to an apoptotic cell a pharmaceutically acceptable composition comprising an activatable probe, wherein said activatable probe comprises a detachable capping moiety conjugated to a self-cyclizing molecule, said self-cyclizing molecule comprising a cysteine moiety, a 2-cyano-6-hydroxyquinoline moiety, an amino luciferin scaffold, and a detectable imaging moiety, wherein the detachable capping moiety has the amino acid sequence L-aspartate-glutamate-valine-aspartate and is selectively cleavable from the self-cyclizing molecule by caspase 3/7, whereupon the activatable probe enters the apoptotic cell, an apotopically-induced caspase 3/7 cleaves the detachable capping moiety from the activatable probe, and said probe aggregates to form the nano-aggregation probe.
A method of detecting an apoptotic cell, the method comprising the steps of:
Dependencies are inferred from the claim text.