A novel interleukin-13 receptor alpha 2-targeted hybrid peptide for effective glioblastoma therapy.

Abstract

We previously designed and reported a novel class of drugs, namely hybrid peptides, which are chemically synthesized and composed of a targeted binding peptide and a lytic-type peptide containing cationic amino acid residues that cause cancer cell death. In the present study, we screened for peptides that bind to interleukin-13 receptor alpha 2 (IL-13Rα2) by using a T7 random peptide phage display library system and isolated several positive phage clones. The A2b11 peptide, which was one of the positive clones, was shown to bind to IL-13Rα2 protein by Biacore analysis and a binding assay using glioblastoma (GB) cell lines. This peptide was linked with a lytic peptide containing a linker sequence to form the IL-13Rα2-lytic hybrid peptide. The IL-13Rα2-lytic hybrid peptide showed cytotoxic activity against GB cell lines in vitro. The IL-13Rα2-lytic hybrid peptide also affected Akt and Erk1/2 activation following treatment with interleukin-13 and induced rapid ATP dynamics in GB cells. Anti-tumor activity of the IL-13Rα2-lytic hybrid peptide was observed in vivo after intratumoral injection in a mouse xenograft model of human GB cells. These results suggest that the IL-13Rα2-lytic hybrid peptide might be a potent therapeutic option for patients with GB.

• Authors: Ryohsuke Kurihara, Tomohisa Horibe, Eiko Shimizu, Aya Torisawa, Arong Gaowa, Masayuki Kohno, Koji Kawakami
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 94 Issue 1 Pg. 1402-1413 (07 2019) ISSN: 1747-0285 [Electronic] England
• PMID: 30903640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Interleukin-13 Receptor alpha2 Subunit
• Peptide Library
• Peptides
• Recombinant Proteins
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Female
• Glioblastoma (drug therapy, pathology)
• Humans
• Interleukin-13 Receptor alpha2 Subunit (antagonists & inhibitors, genetics, metabolism)
• Mice
• Mice, Nude
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Peptide Library
• Peptides (chemistry, metabolism, pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)
• Recombinant Proteins (biosynthesis, chemistry)
• Signal Transduction (drug effects)
• Xenograft Model Antitumor Assays