An Imidazolium-Based Lipid Analogue as a Gene Transfer Agent.

Autor: Paulisch TO; Institute of Organic Chemistry, University of Münster, Corrensstraße 40, 48149, Münster, Germany., Bornemann S; Physical Chemistry I-Biophysical Chemistry, TU Dortmund University, 44221, Dortmund, Germany., Herzog M; Physical Chemistry I-Biophysical Chemistry, TU Dortmund University, 44221, Dortmund, Germany., Kudruk S; Institute of Medical Biochemistry, University of Münster, 48149, Münster, Germany., Roling L; Institute of Organic Chemistry, University of Münster, Corrensstraße 40, 48149, Münster, Germany., Linard Matos AL; Institute of Medical Biochemistry, University of Münster, 48149, Münster, Germany., Galla HJ; Institute of Biochemistry, University of Münster, 48149, Münster, Germany., Gerke V; Institute of Medical Biochemistry, University of Münster, 48149, Münster, Germany., Winter R; Physical Chemistry I-Biophysical Chemistry, TU Dortmund University, 44221, Dortmund, Germany., Glorius F; Institute of Organic Chemistry, University of Münster, Corrensstraße 40, 48149, Münster, Germany.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2020 Dec 18; Vol. 26 (71), pp. 17176-17182. Date of Electronic Publication: 2020 Nov 09.
DOI: 10.1002/chem.202003466
Abstrakt: A dicationic imidazolium salt is described and investigated towards its application for gene transfer. The polar head group and the long alkyl chains in the backbone contribute to a lipid-like behavior, while an alkyl ammonium group provides the ability for crucial electrostatic interaction for the transfection process. Detailed biophysical studies regarding its impact on biological membrane models and the propensity of vesicle fusion are presented. Fluorescence spectroscopy, atomic force microscopy and confocal fluorescence microscopy show that the imidazolium salt leads to negligible changes in lipid packing, while displaying distinct vesicle fusion properties. Cell culture experiments reveal that mixed liposomes containing the novel imidazolium salt can serve as plasmid DNA delivery vehicles. In contrast, a structurally similar imidazolium salt without a second positive charge showed no ability to support DNA transfection into cultured cells. Thus, we introduce a novel and variable structural motif for cationic lipids, expanding the field of lipofection agents.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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