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Research Articles: Therapeutics

A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity

Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

Requests for reprints: Ching-Hsuan Tung, Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th Street, Room 5406, Charlestown, MA 02129. Phone: 617-726-5779; Fax: 617-726-5708. E-mail: tung{at}helix.mgh.harvard.edu.

A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC₅₀ of r7-kla (3.54 ± 0.11 µmol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems. [Mol Cancer Ther 2006;5(8):1944–9]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: L. Quinti and Y. Choi contributed equally to this work.

Received 12/ 6/05; revised 5/15/06; accepted 6/ 6/06.