Novel polyamine-dialkyl phosphate conjugates for gene carriers. Facile synthetic route via an unprecedented dialkyl phosphate.
To develop a novel nonviral gene carrier, three types of polyamine-dialkyl phosphates conjugates were synthesized via an unprecedented synthetic intermediate, dimerized dicetyl phosphate (DCP) anhydride, and the transfection efficiency and the complexation properties of the conjugate-DNA were evaluated. Condensation of DCP by 1,3,5-triisopropylbenzenesulfonyl chloride, TPSCl, gives the dimerized anhydride, which is stable enough to isolate by column chromatography in approximately 90% yield. The anhydride is reactive with various amines, i.e., spermidine, spermine, and polyethylenimine (PEI(1800)), providing corresponding polyamine-DCP conjugates via phosphoramidate linkage. The polyamine-DCP conjugates exhibited moderate transfection efficacy evaluated by beta-galactosidase assay. The conjugate-DNA complex was observed by using an atomic force microscope (AFM), revealing that the PEI(1800)-DCP conjugate, which showed the most efficient transfection, enables the formation of the more compact complex with DNA.
Dewa
Takehisa
T
Materials Science and Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, 466-8555 Japan.
Ieda
Yukari
Y
Morita
Kazuyuki
K
Wang
Li
L
MacDonald
Robert C
RC
Iida
Kouji
K
Yamashita
Keiji
K
Oku
Naoto
N
Nango
Mamoru
M
D000818:Animals; D002478:Cells, Cultured; D003087:Colicins / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010755:Organophosphates / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D011073:Polyamines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions / Q000737:chemistry; D014162:Transfection / Q000295:instrumentation / Q000379:methods*
D003087:Colicins; D010755:Organophosphates; D010710:Phosphates; D011073:Polyamines; D012996:Solutions; D004247:DNA