Drug discovery and diagnostics based on nucleic acid switches that respond to ligand interactions
Targets of particular interest for drug discovery include proteins from HIV and proteins involved in bleeding disorders, angiogenesis, cancer and other proliferative diseases. Biosensors are designed to detect the presence of environmental contaminants, terrorist threats, and proteins involved in chromatin remodeling.
Three-dimensional structures of RNA and RNA-protein complexes from HIV and other drug targets
3D structures are determined primarily by NMR methods. Of special interest are drug leads bound to protein targets where the leads have been discovered using high throughput screens based on molecular switch sensors.
Aptamer discovery and validation
Aptamers are DNA/RNA molecules that have affinities for their targets similar to antibodies. We are developing high throughput screens to simplify aptamer discovery. Microarray methods are used to measure the affinity of aptamers for their targets and to evaluate off-target effects.
We manage the department's NMR facility and share equipment with the neighboring campuses of the SUNY College of Environmental Science and Forestry (ESF) and the SUNY Upstate Medical University. Students in my lab collaborate with members of the SU Chemistry and Biology departments, as well as other laboratories on University Hill. They are also exposed to entrepreneurial activity through Syracuse University’s business incubator center.
Borer, P. N. and Hudson, B. S. (2009) US Patent 7,521,546 "Branched and Multi-Chain Nucleic Acid Switches for Sensing and Screening."
DeCiantis, C. L.; Jensen, D. K.; Hudson, B. S.; Borer, P. N. A Nucleic Acid Switch Triggered by the HIV-1 Nucleocapsid Protein. Biochemistry 2007, 46, 9164-73.
Boudreau, E. A.; Pelczer, I.; Borer, P. N.; Heffron, G. J.; LaPlante, S. R. Changes in Drug 13C NMR Chemical Shifts as a Tool for Monitoring Interactions with DNA. Biophysical Chem. 2004, 109, 333-344.
Yuan, Y.-Q.; Kerwood, D. J.; Paoletti, A. C.; Shubsda, M. F.; Borer, P. N. The Stem of SL1 RNA in HIV-1: Structure and Nucleocapsid Protein Binding for a 1x3 Internal Loop. Biochemistry 2003, 42, 5259-5269.
Shubsda, M. F.; Paoletti, A. C.; Hudson, B. S.; Borer, P. N. Affinities of Packaging Domain Loops in HIV-1 RNA for the Nucleocapsid Protein. Biochemistry 2002, 41, 5276-5282.