Investigation of new properties and applications of quadruplex DNA and development of novel oligonucleotide-based topoisomerase I inhibitors

Abstract

Some sequences of DNA that possess certain guanine or cytosine-riched stretches are capable of associating into four-stranded DNA structures, namely G-quadruplex and i-motif respectively. It has been suggested that some of these quadruplex structures could exist in some biologically important regions of DNA such as at the end of chromosomes and in the regulatory regions of oncogenes. In addition, due to their distinctive structural characteristics, quadruplex structures of DNA have been widely used as building blocks in various nanotechnological applications. With the aim of exploring new properties and applications of quadruplex DNA, we have (1) constructed i-motif DNA-based molecular devices that are operable through variations of their surrounding pH values; (2) developed certain fluorescence-tagged circular G-quadruplexes to be used as molecular probes; and (3) investigated the factors that affect the G-quadruplex that could undergo self-cleavage reactions. Finally, we have designed and synthesized certain dumbbell-shaped oligonucleotides and further examined their inhibitory effect on the activities of human topoisomerase I.