title: The influence of novel gemini surfactants containing cycloalkyl side-chains on the structural phases of DNA in solution.
abstract: Very important to gene therapy is the delivery system of the nucleic acids (called a vector), which will enhance the efficiency of the transport of new DNA into cells whilst protecting against damage. A promising alternative to the currently used viral vectors are the systems based on amphiphilic compounds - lipoplexes. Among them, gemini surfactants, which consist of two hydrophobic chains and two cationic heads connected by a linker - spacer group, appear to be promising candidates. The subject of this study involves two gemini surfactants, alkoxy derivatives of bis-imidazolium quaternary salts, differing in the length of their spacer groups and how they interact with two types of salmon sperm DNA (low and high molecular weight (MW)) or plasmid DNA (pDNA). The mixtures of gemini surfactants with nucleic acids of differing p/n ratios (positive-to-negative charge ratio) were characterised by small angle X-ray scattering (SAXS) of synchrotron radiation, dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and gel electrophoresis techniques. This analysis allows for the selection of the most suitable and promising candidates for non-viral vectors in gene therapy, determination of the conditions needed to form stable complexes, identification of conformational changes in the DNA molecules upon interactions with gemini surfactants and in some cases, determination of the structures formed in these lipoplexes.
authors.affiliation: Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Pietralik
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Kumita
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.affiliation: Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland. Electronic address: mkozak@amu.edu.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kozak
mesh_terms: D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D003516:Cycloparaffins / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D053838:Scattering, Small Angle; D012996:Solutions; D013501:Surface-Active Agents / Q000737:chemistry*; D017356:Synchrotrons; D014961:X-Ray Diffraction
chemical_list: D002412:Cations; D003516:Cycloparaffins; D012996:Solutions; D013501:Surface-Active Agents; D004247:DNA
keywords: CD; Gemini surfactant; Gene therapy; Lipoplex; SAXS