Phongtongpasuk, Siriporn
(2011).
Investigating the interaction of a metallosupra molecular cylinder with nucleic acids.
University of Birmingham.
Ph.D.
Abstract
Chapter 1 reviews the background of nucleic acid structures and drug targeting to nucleic acids. The concept of molecular recognition between drugs and nucleic acids is also discussed. Besides, being a drug target, DNA can be used as material for constructing beautiful architectures. Examples of these DNA nanostructures are presented. In Chapter 2, three way junction recognition by a metallocylinder is shown to occur not only in DNA but also in RNA. The recognition of RNA three way junctions by the metallosupramolecular cylinder, its enantiomers and its analogues are explored. It shows that the cylinders have the ability to bind preferentially to RNA three way junctions and to RNA-DNA hybrids. In addition, a competition assay of nucleic acids to the iron cylinder is examined. It indicates that the iron cylinder may prefer to bind to RNA three way junctions rather than DNA. In Chapter 3, to elucidate the crucial features of the metallosupramolecular cylinder for recognition of the DNA three way junction, an array of cylinder derivatives are screened. The results indicate that the geometry of the cylinder is the key trait for the recognition. Moreover, the electrostatic interaction from the cylinder can enhance the affinity of the recognition. In Chapter 4, the molecular effect of the iron cylinder on the structure of a DNA tetrahedron nanostructure is examined. Several biophysical techniques confirm that the cylinder binds strongly with the nanostructure, thus leading to the unusual style of a very rigid DNA nanostructure. In Chapter 5, to precisely determine the binding affinity of the cylinder to DNA, the development of SPR experiments is described. The results show that the value of the binding affinity obtained from SPR is less than that obtained using the conventional method of ethidium bromide displacement. This is due to the inaccurate measuring of the latter method during the experiment.
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