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Specific uptake and interactions of peptide nucleic acid derivatives with biomimetic membranes


Joshi, Tanmaya; Gasser, Gilles; Martin, Lisandra L; Spiccia, Leone (2012). Specific uptake and interactions of peptide nucleic acid derivatives with biomimetic membranes. RSC Advances, 2:4703-4712.

Abstract

There is a growing interest in understanding the uptake mechanism of metal-containing peptide nucleic acid (PNA) bioconjugates into living cells. In this study, quartz crystal microbalance with dissipation monitoring (QCM-D) has been used to explore the membrane specific uptake and interactions of PNA/peptide/Ru(II) conjugates. For all lipid compositions, the unmodified PNA oligomer and its Ru(II) conjugate were found to traverse freely across the membrane in a trans-membrane manner, causing no significant changes in the membrane structure. The nuclear localised signal peptide (NLS) conjugated sequences showed membrane specific activities. In model mammalian and bacterial-mimetic membranes, rapid trans-membrane insertion was observed followed by a concentration dependent disruption and irreversible structural changes to the membrane system. The variations in the magnitude of the structural changes and in their tendency to facilitate disruption are ascribed to hydrophobicity, the cationic charge introduced on modification of the original PNA backbone as well as the physical state of the model membrane used.

Abstract

There is a growing interest in understanding the uptake mechanism of metal-containing peptide nucleic acid (PNA) bioconjugates into living cells. In this study, quartz crystal microbalance with dissipation monitoring (QCM-D) has been used to explore the membrane specific uptake and interactions of PNA/peptide/Ru(II) conjugates. For all lipid compositions, the unmodified PNA oligomer and its Ru(II) conjugate were found to traverse freely across the membrane in a trans-membrane manner, causing no significant changes in the membrane structure. The nuclear localised signal peptide (NLS) conjugated sequences showed membrane specific activities. In model mammalian and bacterial-mimetic membranes, rapid trans-membrane insertion was observed followed by a concentration dependent disruption and irreversible structural changes to the membrane system. The variations in the magnitude of the structural changes and in their tendency to facilitate disruption are ascribed to hydrophobicity, the cationic charge introduced on modification of the original PNA backbone as well as the physical state of the model membrane used.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:15 March 2012
Deposited On:14 Jan 2013 11:35
Last Modified:07 Dec 2017 14:39
Publisher:R S C Publications
ISSN:2046-2069
Publisher DOI:https://doi.org/10.1039/C2RA20462B

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