Currently, RNA is significantly underutilized as a potential target for drug development: most likely because there exists a lack of basic knowledge about how one should design a molecule to target a folded RNA. In our research, the RNA-binding properties of sidechain-functionalized polyamines are being examined with two important RNA targets: TAR RNA and RRE RNA of HIV. Molecules that bind to these RNAs can potentially shut down replication of the virus. The basic knowledge that will be developed from this work will ultimately be applicable to other RNA targets, and will provide a general set of guidelines for designing molecules that selectively bind a folded RNA structure. Over the past year, we have established a new library of molecules that can be screened for selective binding to TAR RNA, and we have validated this screening strategy using a number of basic biochemical methods. We are still optimizing our initial leads for better binding affinity. We have also initiated a collaboration with a cell biology group to study the activity of these molecules in HIV infected cells. In addition, we are starting a collaboration with NMR spectroscopists to study the conformation of RNA when our molecule binds.
| Xu, Qun; Appella, Daniel H (2008) Aziridination of aliphatic alkenes catalyzed by N-heterocyclic carbene copper complexes. Org Lett 10:1497-500 |
| Lawton, Graham R; Appella, Daniel H (2004) Nonionic side chains modulate the affinity and specificity of binding between functionalized polyamines and structured RNA. J Am Chem Soc 126:12762-3 |
