An Artificial Copper Complex Incorporating a Cell-Penetrating Peptide Inhibits Nuclear Factor-κB (NF-κB) Activation

Yosuke Kanemaru; Yumi Momiki; Saori Matsuura; Tatsufumi Horikawa; Jin Gohda; Jun-ichiro Inoue; Yoshinari Okamoto; Mikako Fujita; Masami Otsuka

doi:10.1248/cpb.59.1555

Notes

An Artificial Copper Complex Incorporating a Cell-Penetrating Peptide Inhibits Nuclear Factor-κB (NF-κB) Activation

Yosuke Kanemaru, Yumi Momiki, Saori Matsuura, Tatsufumi Horikawa, Jin Gohda, Jun-ichiro Inoue, Yoshinari Okamoto, Mikako Fujita, Masami Otsuka

Author information

Yosuke Kanemaru
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University
Yumi Momiki
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University
Saori Matsuura
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University
Tatsufumi Horikawa
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University
Jin Gohda
Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University
Jun-ichiro Inoue
Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University
Yoshinari Okamoto
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University
Mikako Fujita
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo
Masami Otsuka
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University

Keywords: nuclear factor-κB (NF-κB), copper complex, cell-penetrating peptide, Tat

JOURNAL FREE ACCESS

2011 Volume 59 Issue 12 Pages 1555-1558

DOI https://doi.org/10.1248/cpb.59.1555

Details

Abstract

Nuclear factor-κB (NF-κB) is an inducible transcription factor activated by a variety of cytokines, and promotes the transcription of genes involved in cancer, inflammation, autoimmune disease, and viral infection, among others. Because of its involvement in numerous disease processes, considerable research has focused on NF-κB as a potential drug target. We previously reported that cupric ion (Cu²⁺) blocks NF-κB activation. However, Cu²⁺ is unsuitable for drug applications. The copper complex of an artificial peptide HPH-Pep (HPH-Pep-Cu²⁺) was a promising alternative, but it did not easily cross the cell membrane. We report the development of a NF-κB inhibiting Cu²⁺ complex with improved cell-penetrating activity arising from the coupling of a Tat peptide to HPH-Pep-Cu²⁺.

Corresponding author

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