title: Photosensitive Peptidomimetic for Light-Controlled, Reversible DNA Compaction.
abstract: Light-induced DNA compaction as part of nonviral gene delivery was investigated intensively in the past years, although the bridging between the artificial light switchable compacting agents and biocompatible light insensitive compacting agents was not achieved until now. In this paper, we report on light-induced compaction and decompaction of DNA molecules in the presence of a new type of agent, a multivalent cationic peptidomimetic molecule containing a photosensitive Azo-group as a branch (Azo-PM). Azo-PM is synthesized using a solid-phase procedure during which an azobenzene unit is attached as a side chain to an oligo(amidoamine) backbone. We show that within a certain range of concentrations and under illumination with light of appropriate wavelengths, these cationic molecules induce reversible DNA compaction/decompaction by photoisomerization of the incorporated azobenzene unit between a hydrophobic trans- and a hydrophilic cis-conformation, as characterized by dynamic light scattering and AFM measurements. In contrast to other molecular species used for invasive DNA compaction, such as widely used azobenzene containing cationic surfactant (Azo-TAB, C4-Azo-OCX-TMAB), the presented peptidomimetic agent appears to lead to different complexation/compaction mechanisms. An investigation of Azo-PM in close proximity to a DNA segment by means of a molecular dynamics simulation sustains a picture in which Azo-PM acts as a multivalent counterion, with its rather large cationic oligo(amidoamine) backbone dominating the interaction with the double helix, fine-tuned or assisted by the presence and isomerization state of the Azo-moiety. However, due to its peptidomimetic backbone, Azo-PM should be far less toxic than photosensitive surfactants and might represent a starting point for a conscious design of photoswitchable, biocompatible vectors for gene delivery.
authors.affiliation: Institute of Physics and Astronomy, University of Potsdam , 14476 Potsdam, Germany.|Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Selina
authors.initials: S
authors.lastname: Schimka
authors.affiliation: Institute of Physics and Astronomy, University of Potsdam , 14476 Potsdam, Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Santer
authors.affiliation: Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Mujkić-Ninnemann
authors.affiliation: Humboldt-Universität zu Berlin, 12489 Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Bléger
authors.affiliation: Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Hartmann
authors.affiliation: Theory and Bio-Systems Group, Max Planck Institute of Colloids and Interfaces , 14424 Potsdam, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Wehle
authors.affiliation: Theory and Bio-Systems Group, Max Planck Institute of Colloids and Interfaces , 14424 Potsdam, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lipowsky
authors.affiliation: Theory and Bio-Systems Group, Max Planck Institute of Colloids and Interfaces , 14424 Potsdam, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Santer
mesh_terms: D001391:Azo Compounds / Q000737:chemistry* / Q000528:radiation effects; D011232:Chemical Precipitation; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000528:radiation effects; D000067493:Dynamic Light Scattering; D018014:Gene Transfer Techniques; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D057786:Peptidomimetics / Q000737:chemistry* / Q000528:radiation effects; D055668:Photochemical Processes; D013501:Surface-Active Agents / Q000737:chemistry* / Q000528:radiation effects
chemical_list: D001391:Azo Compounds; D057786:Peptidomimetics; D013501:Surface-Active Agents; D004247:DNA; C009850:azobenzene