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Zusammenfassung:
Light induced DNA compaction as part of non-viral 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 wave lengths, 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 counter ion, 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 ?genuine? photosensitive surfactants, and might represent a starting point for a conscious design of photoswitchable, biocompatible vectors for gene delivery.
