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In vitro membrane penetration of modified peptide nucleic acid (PNA)

Malin Ardhammar (Institutionen för fysikalisk kemi) ; Bengt Nordén (Institutionen för fysikalisk kemi) ; P.E. Nielsen ; Bo Malmström ; P. Wittung-Stafshede
Journal of Biomolecular Structure & Dynamics (0739-1102 ). Vol. 17 (1999), 1, p. 33-40.
[Artikel, refereegranskad vetenskaplig]

Efficient cellular uptake is crucial for the success of any drug directed towards targets inside cells. Peptide nucleic acid (PNA), a DNA analog with a promising potential as a gene-directed drug, has been shown to display slow membrane penetration in cell cultures. We here used liposomes as an in vitro model of cell membranes to investigate the effect on penetration of a PNA molecule colvalently modified with a lipophilic group, an adamantyl moiety. The adamantyl attachment was found to increase the membrane-penetration rate of PNA three-fold, as compared to corresponding unmodified PNA. From the penetration behaviour of a number of small and large molecules we could conclude that passive diffusion is the mechanism for liposome-membrane passage. Flow linear dichroism (LD) of the modified PNA in presence of rod-shaped micelles, together with octanol-water distribution experiments. showed that the adamantyl-modified PNA is amphiphilic; the driving force behind the observed increased membrane-penetration rate appears to be an accumulation of the PNA in the lipid double layer.

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Denna post skapades 2011-02-18. Senast ändrad 2011-06-21.
CPL Pubid: 136941


Institutioner (Chalmers)

Institutionen för fysikalisk kemi (1900-2003)


Nanovetenskap och nanoteknik
Fysikalisk kemi

Chalmers infrastruktur