As can be seen from the molecule graphics above, my research interests involve nucleoside chemistry and the design of nucleosides as antiviral and antitumor agents. We have designed a series of nucleoside analogs that incorporate significant aspects of the natural nucleosides, but that have been changed in ways that are expected to lead to biological activity. Many of the enzymes which are involved in the processing of nucleosides require the nucleoside to fold into a relatively unstable conformation. We have designed nucleoside analogs which should be more stable in this required conformation than are the natural nucleosides, and therefore may interact effectively with these enzymes. Because the controlling enzymes of many nucleoside processing sequences are less selective in transformed cells or virally infected cells, it is hoped that abnormal cells will be more likely to process and use our analogs than normal cells, and that this will lead to selectivity in the biological activity.

We are also developing methods to easily determine the solution conformations of nucleosides, so that we can test our predictions about the shapes of our analogs.

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