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Novel Peptides for More Efficient Delivery of Therapeutic and Imaging Agents

This invention is a novel composition of matter that disrupts endosomes allowing for the release of biologically active agents into the cytosol.

Viruses can utilize endosomes and lysosomes to enter the cytosol of cells. In contrast, small molecule ligands that are transported into the cell via endosomes are often trapped in the late endosomes and/or lysosomes and are broken down prior to asserting their biological function. The current invention overcomes this problem by utilizing a conformationally-constrained kinked peptide to disrupt the endosome, allowing the release of active small molecules into the cytoplasm and nucleus of cells. The small molecule ligand can be attached to a targeting group or the peptide via a disulfide linker to allow the ligand to be transported as cargo into the cell. Further, the peptide can also be attached to a targeting group to allow the cargo to be released and reach the desired destination. By disrupting endosomes containing the ligand, the ligand is released into the cytosol.

APPLICATIONS: 

The current invention utilizes a conformationally-constrained kinked peptide to disrupt endosomes allowing for more efficient transport of therapeutic or imaging agents into the cell. The agents transported can be drugs such as anti-cancer or anti-viral agents.

HOW IT WORKS:

The conformationally-constrained kinked portion of the peptide disrupts the membrane of the endosome. The disruption in the membrane allows the endosome to release the biologically relevant compound into the cytosol.

BENEFITS: 

The invention allows for more efficient transfer of the active form of biologically relevant compounds to the cytosol. This decreases the dose required for effective treatment.

WHY IT IS BETTER:

The current invention utilizes well known linker chemistry to allow a variety of targeting or other groups to be added to the conformationally-constrained kinked peptide.

OTHER APPLICATIONS:

This technology could also be used to transfer other agents into the cell unharmed by the possible degradation that could occur in late endosomes or lysosomes. This can improve imaging of such cells.

Additional Details

Owner

University of Kansas

Intellectual Property Protection

Pending Patent



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