Synthesis and transfection efficiencies of new lipophilic polyamines

    Authors

    R. A. Gardner; M. Belting; K. Svensson;O. Phanstiel

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    CATIONIC LIPIDS; VIRAL VECTORS; GENE DELIVERY; MOLECULAR REQUIREMENTS; BIOLOGICAL EVALUATION; SELECTIVE DELIVERY; DNA-TRANSFECTION; CELLS; TRANSPORTERS; THERAPEUTICS; Chemistry, Medicinal

    Abstract

    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 N(1) 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 (14)C-spermine uptake (IC(50) similar to 10 mu M), 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.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    50

    Issue/Number

    2

    Publication Date

    1-1-2007

    Document Type

    Article

    Language

    English

    First Page

    308

    Last Page

    318

    WOS Identifier

    WOS:000243535600015

    ISSN

    0022-2623

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