Novel Peptide as Diagnostic and Therapeutic Tool for Cancer


Project ID: MBC00101


Novelty:  A novel cyclic peptide, L1AD3, which serves as apoptosis-inducing cytotoxic agent and is useful against several types of cancers, particularly against leukemic T-cells and B-cells. The biotinylated analog serves to identify cancer cells via binding specifically to Leukemic T- Lymphocytes. 


Value Proposition:

The disclosed invention embodies a beta-sheet cyclic peptide, L1AD3, which binds to tumor cell membrane and prevents cell division. The peptide composition shows no toxicity toward normal human white blood cells nor does it depolarize heart muscle. This peptide is an analog of and structurally resembles the parent toxin from which it was derived, cytotoxin-III from Taiwan Cobra Naja naja atra. The other advantages of this technology include:

·       The peptide induces or promotes apoptosis.

·       Use of D- as well as L- amino acids to synthesize peptide.

·       Exhibits minimal toxic effects against normal human cells.

·       Induces apoptosis as a mechanism of causing cell death.

·       N-terminal biotinylation of the peptide facilitate identification of cancer cells and thus serves as a diagnostic tool.



Dr. Channing Hinman and Dr. Charles Smith at The University of Toledo have synthesized a small 14-mer cyclic peptide and demonstrated its biologic activity as a cytotoxic agent and for inducing apoptosis in cancer cells, leukemic T-cells and B-cells. The sequence is identical to N-terminal 14 amino acids in cytotoxin III (CTX) of Taiwan cobra. The scientists demonstrated that this peptide does not permeabilize cells from either the Jurkat or the CEM human leukemic T-lymphocyte lines unlike the activity of parent CTX, which at micromolar concentrations drastically perturbs the plasma membrane and render them permeable to fluorescent dyes. They further demonstrated that the peptide stops tumor cell division in both Jurkat and CEM cells by inhibiting the incorporation of thymidine, with an EC50 of approximately 5 µm. The peptide composition shows no toxicity toward normal human white blood cells nor does it depolarize heart muscle.

 To investigate peptide binding to cell surfaces, the scientists modified the peptide by N-terminal biotinylation. A biotin-adivin sorbent assay was performed and when binding was measured by fluorescence spectroscopy using CEM cells in suspension, along with Avidin-FITC, fluorescence was shown to increase by 48% over cells not incubated with biotinylated peptide prior to washing. Also, the studies revealed that that the biotinylated peptide did not appreciably bind to normal human peripheral blood lymphocytes, thus making it a diagnostic tool, specifically for cancer cells.

Application: In diagnosis and treatment of cancerous cells.

IP Status: U.S. Patent #7,105,635


1.      A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines.

2.      Evidence that L1AD3, an apoptosis-inducing cyclic peptide, binds a leukemic T-cell membrane protein receptor.

3.      Selective cytolysis by a protein toxin as a consequence of direct interaction with the lymphocyte plasma membrane.

Related technology: D2009-47


Patent Information:
For Information, Contact:
Mark Fox
Patent Technology Associate
The University of Toledo
Channing Hinman
Charles Smith
Cobra Toxin
Cyclic peptide