Arginine carrier peptide bearing Ni(II) chelator to promote cellular uptake of histidine-tagged proteins.
Arginine-rich peptide-mediated protein delivery into living cells is a novel technology for controlling cell functions with therapeutic potential. In this report, a novel approach for the intracellular delivery of histidine-tagged proteins was introduced where a Ni(II) chelate of octaarginine peptide bearing nitrilotriacetic acid [R8-NTA-Ni(II)] was used as a membrane-permeable carrier molecule. Significant internalization of histidine-tagged enhanced green fluorescent protein (EGFP) into HeLa cells was observed by confocal microscopic observation in the presence of R8-NTA-Ni(II). Nuclear condensation characteristic in apoptotic cell death was also induced in the cells treated with a histidine-tagged apoptosis-inducing peptide [pro-apoptotic domain peptide (PAD)], indicating that the cargo molecules really went through the membrane to reach the cytosol. The apoptosis-inducing activity of the peptide thus delivered was compared with that of the PAD peptide covalently connected with the octaarginine peptide.
Futaki
Shiroh
S
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. futaki@scl.kyoto-u.ac.jp
Niwa
Miki
M
Nakase
Ikuhiko
I
Tadokoro
Akiko
A
Zhang
Youjun
Y
Nagaoka
Makoto
M
Wakako
Naoya
N
Sugiura
Yukio
Y
D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D015195:Drug Design; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D009532:Nickel / Q000737:chemistry*; D009571:Nitrilotriacetic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*
D004337:Drug Carriers; D009842:Oligopeptides; D010455:Peptides; C448619:octaarginine; D049452:Green Fluorescent Proteins; D006639:Histidine; D009532:Nickel; D001120:Arginine; D009571:Nitrilotriacetic Acid