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Synthesis and transfection efficiencies of new lipophilic polyamines

Gardner, Richard Andrew; Belting, Mattias LU ; Svensson, Katrin LU and Phanstiel, Otto (2007) In Journal of Medicinal Chemistry 50(2). p.308-318
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 C-14-spermine uptake (IC50 similar to 10 mu M), which implied that 26 is... (More)
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 C-14-spermine uptake (IC50 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
50
issue
2
pages
308 - 318
publisher
American Chemical Society (ACS)
external identifiers
  • wos:000243535600015
  • scopus:33846469404
ISSN
1520-4804
DOI
10.1021/jm0607101
language
English
LU publication?
yes
id
9593a7e2-caca-4465-9f66-04eb7e5db883 (old id 677306)
date added to LUP
2007-12-11 14:50:54
date last changed
2017-10-01 03:58:08
@article{9593a7e2-caca-4465-9f66-04eb7e5db883,
  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 C-14-spermine uptake (IC50 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.},
  author       = {Gardner, Richard Andrew and Belting, Mattias and Svensson, Katrin and Phanstiel, Otto},
  issn         = {1520-4804},
  language     = {eng},
  number       = {2},
  pages        = {308--318},
  publisher    = {American Chemical Society (ACS)},
  series       = {Journal of Medicinal Chemistry},
  title        = {Synthesis and transfection efficiencies of new lipophilic polyamines},
  url          = {http://dx.doi.org/10.1021/jm0607101},
  volume       = {50},
  year         = {2007},
}