Date of Award
Master of Science (MS)
W. David Wilson - Committee Chair
Claudia Sissi - Committee Member
David Boykin - Committee Member
Giovanni Gadda - Committee Member
Manlio Palumbo - Committee Member
Markus Germann - Committee Member
G-quadruplex structures are found in important regions of the eukaryotic genome, such as telomeres and regulatory sequences of genes, and are likely to play important roles in regulation of biological events. The significant structural differences with duplex DNA make quadruplex DNA a very attractive target for anticancer drug design. The purpose of this study is to explore conformational space in a series of heterocyclic cations to discover novel structural motifs that can selectively bind and stabilize specific G-quadruplex arrangements. A variety of biophysical techniques such as thermal melting experiments, biosensor surface plasmon resonance, circular dichroism, fluorescence displacement assay and mass spectrometry were employed to evaluate the affinity of the compounds and their recognition properties. The screening of the molecules allowed the identification of not only selective G-quadruplex ligands but also potential quadruplex groove binders. These results can be useful for the development of new efficient telomerase inhibitors which are endowed with pharmacological activity.
Musetti, Caterina Livia, "Heterocyclic Cations as Potential Anticancer Agents: An Approach that Targets G-quadruplex with Different Binding Modes" (2010). Chemistry Theses. Paper 26.