Certain guanosine-rich phosphodiester oligodeoxynucleotides (GROs) can inhibit cancer cell proliferation and one of the GROs is currently in clinical trials. Their biological activity depends on their formation of stable quadruplex structures that are recognized by nucleolin protein. The goal of this research project is to determine the relationship between the biological properties of GROs and their structural characteristics. A series of G-quartet forming sequences have been examined for their abilities to inhibit cancer cell proliferation and to bind to nucleolin. These oligonucleotides have also been characterized by various biophysical techniques. Nucleolin binding was found to be the best predictor of anticancer activity. The results also indicate that multiple approaches are needed to characterize the molecular structure of quadruplex oligonucleotides.
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