Unsaturated fatty acid-conjugated CP2c-targeting peptide-based anticancer drug

CP2c-targeting peptide anticancer conjugate with enhanced in vivo stability via DHA conjugation

This technology is a CP2c-targeting peptide-DHA conjugate, featuring a two-glycine linker attached to the N-terminus of a six-amino acid peptide that binds to the transcription factor CP2c, with the unsaturated fatty acid DHA conjugated to the linker. If necessary, a cell-penetrating peptide can be added to the C-terminus of the peptide to enhance delivery into cancer cells.

Existing protein and peptide anticancer drugs often cause significant side effects by affecting normal cells, lose efficacy against drug-resistant cancer cells, and suffer from short in vivo half-lives. Previous attempts to improve stability by attaching palmitic acid, a saturated fatty acid, were limited because the fatty acids clumped together to form micelles, blocking both albumin binding and cell penetration, which actually reduced the effectiveness compared to the peptide alone.

This technology utilizes DHA, which does not form micelles, to increase blood stability while preserving the function of the cell-penetrating peptide, and modifies the C-terminus of the peptide with an amine group to slow degradation. It works by inhibiting the formation of the transcription factor complex containing CP2c, thereby inducing cancer-specific cell death. It can be applied to targeted anticancer drugs for solid tumors such as liver cancer, peptide therapeutics for drug-resistant cancer, and anticancer dietary supplements, enabling the development of versatile peptide anticancer drugs that reduce damage to normal cells and overcome short half-life issues.

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Key Features:

• Transcription factor CP2c-targeting peptide consisting of the amino acid sequence represented by SEQ ID NO: 2
• Linker peptide consisting of two glycines bound to the N-terminus of the CP2c-targeting peptide
• Unsaturated fatty acid DHA forming a conjugate by binding its carboxyl group to the amino group at the N-terminus of the linker peptide
• Cell-penetrating peptide represented by SEQ ID NO: 3 bound to the C-terminus of the CP2c-targeting peptide

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This invention was developed with support from the Ministry of Science and ICT for the development of CP2c-targeting peptide-based anticancer drugs for the treatment of intractable cancers.

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