Fragment-based screening and lead development can be a fast, reliable and efficient means of obtaining novel compounds for early stage drug design. As a graduate student, my chief contribution to the Varani Group was the initiation and implementation of fragment-based screening methods by NMR spectroscopy. I conducted pilot studies with human thymidylate synthase and a uridylyl transferase from Trypanosoma brucei, demonstrating that these techniques are sufficiently sensitive to determine selectivity, even at the fragment level. I also executed follow-up experiments with a panel of fragment hits to confirm their specificity, estimate their affinity and approximate their binding conformations when bound. Results from these studies have produced promising lead scaffolds which are currently being utilized in the design phase for potential therapeutic applications.

New and more diverse biological targets are now being screened with this approach, including a functional, non-coding RNA molecule from the HIV genome and a kinetochore protein involved in regulating mitotic cell division.