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

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Item Type:	Article
Title:	Enhancement of intracellular concentration and biological activity of PNA after conjugation with a cell-penetrating synthetic model peptide
Creators Name:	Oehlke, J., Wallukat, G., Wolf, Y., Ehrlich, A., Wiesner, B., Berger, H. and Bienert, M.
Abstract:	In order to evaluate the ability of the cell-penetrating α-helical amphipathic model peptide KLALKLALKALK AALKLA-NH2 (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/orphaniti 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 influences of serum.
Keywords:	Cell-Penetrating Peptides, Cellular Uptake, PNA-peptide Conjugates, Animals, Rats
Source:	European Journal of Biochemistry
ISSN:	0014-2956
Publisher:	Blackwell Publishing
Volume:	271
Number:	14
Page Range:	3043-3049
Date:	1 January 2004
Official Publication:	https://doi.org/10.1111/j.1432-1033.2004.04236.x
PubMed:	View item in PubMed

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