Synthesis and transfection efficiencies of new lipophilic polyamines.
A homologous series of lipophilic polyamines was synthesized and evaluated for DNA delivery and transfection efficiency. The series contained 1,4-butanediamine, 1,8-octanediamine, 2-[2-(2-amino-ethoxy)-ethoxy]-ethylamine, homospermidine, and homospermine covalently attached via their N1 terminus to a 3,4-bis(oleyloxy)-benzyl motif. In addition, homospermidine and homospermine were also attached via amide linkers. The homospermidine derivatives (i.e., benzyl tether 25 and benzamide tether 27) showed a 3-fold and 4-fold respective enhancement in delivery of AlexaFluor-488-labeled DNA over the butanediamine analogue 22. Homospermine derivative 26 was shown to inhibit 14C-spermine uptake (IC50 approximately 10 microM), which implied that 26 is able to compete effectively for polyamine recognition sites on the cell surface. This study demonstrated that the number and position of the positive charges along the polyamine scaffold plays a key role in DNA delivery and in determining the transfection efficiency.
Gardner
Richard Andrew
RA
Department of Chemistry, University of Central Florida, Orlando, Florida 32816-2366, USA.
Belting
Mattias
M
Svensson
Katrin
K
Phanstiel
Otto
O
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008055:Lipids / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013096:Spermine / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D004337:Drug Carriers; D008055:Lipids; C086724:Lipofectamine; D011073:Polyamines; D049452:Green Fluorescent Proteins; D013096:Spermine; D004247:DNA