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Dextran-spermine conjugate: an efficient vector for gene delivery
Authors:T. Azzam  H. Eliyahu  A. Makovitzki  A.J. Domb
Affiliation:Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel, Fax: +972-26758959
Abstract:Cationic Polysaccharides based on oligoamine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextran with 40 kDa in average molecular weight was oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in relatively high yields (∼90%). The oxidized dextran was reacted by reductive animation with various oligoamines of 2 to 4 amino groups to obtain the corresponding imine-conjugates. These water-soluble polymers were then reduced by excess of sodium borohydride to obtain the corresponding amine-conjuagtes in 30-40% overall yield. The electrostatic interactions of the representative polycations with plasmid DNA were evaluated as a function of charge ratio (+/−, polymer/DNA) and ionic strength of the medium applying the ethidium-bromide quenching assay. Although most synthetic polycations formed stable complexes with Plasmid DNAs, only the dextran-spermine conjugate of a defined amino content and molecular weight was able to transfect cells with high efficiency.
Keywords:dextran  polyamines  polyelectrolytes  reductive-amination  spermine
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