Design and synthesis of a peptide-PEG transporter tool for carrying adenovirus vector into cells.
The adenovirus vector is a promising carrier for the efficient transfer of genes into cells via the coxackie-adenovirus receptor (CAR) and integrins (alphavbeta3 and alphavbeta5). The clinical use of the adenovirus vector remains problematic however. Successful administration of this vector is associated with side effects because antibodies to this vector are commonly found throughout the human body. To make the adenovirus vector practicable for clinical use, it is necessary to design an auxiliary transporter. The present study describes the use of Arg-Gly-Asp(RGD)-related peptide, a peptide that binds to integrins, as an auxiliary transporter to aid efficient transport of adenovirus vector. Furthermore, poly(ethylene glycol) (PEG) was also used as a tool to modify the adenovirus such that the risk of side effects incurred during clinical application was reduced. The present study describes the design, preparation and use of (acetyl-Tyr-Gly-Gly-Arg-Gly-Asp-Thr-Pro-(beta)Ala)(2)Lys-PEG-(beta)Ala-Cys-NH(2)[(Ac-YGGRGDTP(beta)A)(2)K-PEG-(beta)AC] as an efficient peptide-PEG transporter tool for carrying adenovirus vector into cells. (Ac-YGGRGDTP(beta)A)(2)K-PEG-(beta)AC was coupled with 6-maleimidohexanoic acid N-hydroxysuccinimide ester and the resulting 6-[(Ac-YGGRGDTP(beta)A)(2)K-PEG-(beta)AC-succinimido]hexanoic acid N-hydroxysuccinimide ester reacted with adenovirus. The modified adenovirus with the peptide-PEG hybrid exhibited high gene expression even in a CAR-negative cell line, DC2.4.
Maeda
Mitsuko
M
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
Kida
Shinya
S
Hojo
Keiko
K
Eto
Yusuke
Y
Gaob
Jian-Qing
JQ
Kurachi
Shinnosuke
S
Sekiguchi
Fumiko
F
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
Kawasaki
Koichi
K
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D002460:Cell Line; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
D004337:Drug Carriers; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid