title: A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity.
abstract: 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 IC(50) of r7-kla (3.54 +/- 0.11 micromol/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.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th Street, Room 5406, Charlestown, 02129, USA.
authors.forename: Benedict
authors.initials: B
authors.lastname: Law
authors.forename: Luisa
authors.initials: L
authors.lastname: Quinti
authors.forename: Yongdoo
authors.initials: Y
authors.lastname: Choi
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D018675:Toxicity Tests; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins