Structural analysis of DNA complexation with cationic lipids

Regis Marty, Christophe N. N'soukpoé-Kossi, David Charbonneau, Carl Maximilian Weinert, Laurent Kreplak, Heidar Ali Tajmir-Riahi

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

154 Citas (Scopus)

Resumen

Complexes of cationic liposomes with DNA are promising tools to deliver genetic information into cells for gene therapy and vaccines. Electrostatic interaction is thought to be the major force in lipid-DNA interaction, while lipid-base binding and the stability of cationic lipid-DNA complexes have been the subject of more debate in recent years. The aim of this study was to examine the complexation of calf-thymus DNA with cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammoniumbromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE), at physiological condition, using constant DNA concentration and various lipid contents. Fourier transform infrared (FTIR), UV-visible, circular dichroism spectroscopic methods and atomic force microscopy were used to analyse lipid-binding site, the binding constant and the effects of lipid interaction on DNA stability and conformation. Structural analysis showed a strong lipid-DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of KChol = 1.4 (±0.5) × 104M-1, KDDAB = 2.4 (±0.80) × 104M-1, KDOTAP = 3.1 (±0.90) × 104 M1 and KDOPE = 1.45 (±0.60) × 104M1. The order of stability of lipid-DNA complexation is DOTAP>DDAB>DOPE>Chol. Hydrophobic interactions between lipid aliphatic tails and DNA were observed. Chol and DOPE induced a partial B to A-DNA conformational transition, while a partial B to C-DNA alteration occurred for DDAB and DOTAP at high lipid concentrations. DNA aggregation was observed at high lipid content.

Idioma originalEnglish
Páginas (desde-hasta)849-857
Número de páginas9
PublicaciónNucleic Acids Research
Volumen37
N.º3
DOI
EstadoPublished - 2009

Nota bibliográfica

Funding Information:
Natural Sciences and Engineering Research Council of Canada (NSERC). Funding for open access charge has been waived by Oxford University Press.

ASJC Scopus Subject Areas

  • Genetics

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