Modular assembly of functional DNA-based systems

PhD ceremony: Ms. N. Sancho Oltra, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Modular assembly of functional DNA-based systems

Promotor(s): prof. J.G. Roelfes, prof. B.L. Feringa

Faculty: Mathematics and Natural Sciences

 

The specific interaction between the bases of the DNA via hydrogen bonding allows for the assembly of predictable structures of variable complexity based on DNA. The work described in this thesis follows a modular assembly approach for the construction of novel functional systems based on DNA structures. This approach makes use of oligonucleotides with covalently linked functional molecules in combination with unfunctionalized oligonucleotides. The resulting DNA-based systems showed application in the fields of catalysis, synthesis, molecular sensing and light harvesting.

The construction of a DNA-based catalyst with a covalently linked metal complex is described. Using the optimized catalyst, high ee’s and conversions were obtained in the asymmetric copper (II)-catalyzed Diels Alder reaction in water.

The development of an artificial ribosome based on amino acids covalently linked to oligonucleotides complementary to a DNA template was also investigated. No peptide coupling was observed, therefore an optimized system is required.

The catalytic activity of a split enzyme was modulated by DNA hybridization. The approach makes use of protein fragments covalently linked to oligonucleotides complementary to a DNA template. The application of this enzymatic system in the creation of a molecular sensor has been investigated in combination with an ATP aptamer. The binding of ATP triggers the liberation of a DNA sequence necessary for the hybridization of the enzymatic system.

Finally, a construction of a light harvesting system based on DNA G-quadruplexes is described. The particular structure of DNA allows for the placement of donor and acceptor molecules for energy transfer to take place.