PhD ceremony Ms. L. Gjonaj: Chemically modified DNA: methods and applications

PhD ceremony: Ms. L. Gjonaj

Dissertation: Chemically modified DNA: methods and applications

Promotor(s): prof. J.G. Roelfes

Faculty: Mathematics and Natural Sciences

DNA is a fascinating biopolymer which can be manipulated easily and through base-pairing the oligonucleotides can assemble into complex and multifunctional structures. The aim of this research was the development of new methodologies to chemically modify DNA. Various functionalities were attached to DNA, and the new DNA based scaffolds were used for applications in catalysis, as DNA-based surfactants and for modulating the behavior of ion channel forming peptides.

In chapter 2, a new chemo-selective methodology to modify DNA is described. Alkoxylamines were used to selectively functionalize cytosine in single stranded DNA and the products were further derivatized using bioorthogonal reactions.

In chapter 3 a novel design approach to DNA-based hybrid catalysts involving covalent anchoring of bifunctional heterobimetallic complexes by making use of the strong DNA-binding of cisplatin derivatives is reported.

In chapter 4, platinum(II) complexes were applied to modify DNA covalently with long alkyl chains and to build new DNA-based surfactants. Furthermore, the aggregation properties of this class of surfactant were investigated.

In chapter 5, the oligomerization process of the ion channel forming peptide alamethicin was modulated by a covalently attached DNA strands. These hybrids showed an increase of the life times and in the stabilization of one conductance state of the ion channels.

In chapter 6, a DNA G-quadruplex based surfactant, which showed amphiphilic behavior and assembled into micelles and fibers in solution, is described.

Finally, in chapter 7 an overview of the research accomplished in this thesis is presented and future perspectives are discussed.