Title

Synthesis And Transfection Efficiencies Of New Lipophilic Polyamines

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 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 ∼ 10 μM), 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. © 2007 American Chemical Society.

Publication Date

1-25-2007

Publication Title

Journal of Medicinal Chemistry

Volume

50

Issue

2

Number of Pages

308-318

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jm0607101

Socpus ID

33846469404 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/33846469404

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