Enhancement of intracellular concentration and biological activity of PNA after conjugation with a cell-penetrating synthetic model peptide

European Journal of Biochemistry
Johannes OehlkeMichael Bienert

Abstract

In order to evaluate the ability of the cell-penetrating alpha-helical amphipathic model peptide KLALKLALKALKAALKLA-NH(2) (MAP) to deliver peptide nucleic acids (PNAs) into mammalian cells, MAP was covalently linked to the 12-mer PNA 5'-GGAGCAGGAAAG-3' directed against the mRNA of the nociceptin/orphanin FQ receptor. The cellular uptake of both the naked PNA and its MAP-conjugate was studied by means of capillary electrophoresis combined with laser-induced fluorescence detection, confocal laser scanning microscopy and fluorescence-activated cell sorting. Incubation with the fluorescein-labelled PNA-peptide conjugate led to three- and eightfold higher intracellular concentrations in neonatal rat cardiomyocytes and CHO cells, respectively, than found after exposure of the cells to the naked PNA. Correspondingly, pretreatment of spontaneously-beating neonatal rat cardiomyocytes with the PNA-peptide conjugate and the naked PNA slowed down the positive chronotropic effect elicited by the neuropeptide nociceptin by 10- and twofold, respectively. The main reasons for the higher bioavailability of the PNA-peptide conjugate were found to be a more rapid cellular uptake in combination with a lowered re-export and resistance against influ...Continue Reading

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Mar 28, 2009·International Journal of Molecular Sciences·Sandra VeldhoenTobias Restle
Jun 15, 2010·Human Molecular Genetics·Refik KayaliCarmen Bertoni
Dec 12, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Gisela TünnemannM Cristina Cardoso
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