Organic Chemistry Seminar: Professor Benjamin Miller, University of Rochester Medical Center, Sapp Center Lecture Hall, 4:30pm (Host: Eric Kool, Paul Wender)
About the Seminar:
"Natural Products-Inspired Dynamic Combinatorial Recognition of RNA"
Sequence-selective RNA recognition represents an outstanding unsolved problem for the field of Bioorganic Chemistry. In contrast to DNA, there are no heuristics that can map an RNA sequence to a synthetic compound that binds only that sequence. Because of the ever-increasing pace of discovery of RNAs with relevance to basic biology and disease, it has become clear that the development of general methods for the generation of bioactive RNA-binding compounds is a critical need.
We have developed Resin-Bound Dynamic Combinatorial Chemistry (RBDCC) as a method for addressing this challenge. RBDCC allows the rapid in situ synthesis and screening of large (>11,000-compound) libraries without the analytical challenges of “traditional” solution-phase dynamic combinatorial libraries. Using the structure of naturally occurring bisintercalating peptide antibiotics as a starting point, we have applied the RBDCC concept to several RNA targets, including one critical to the life cycle of HIV, and another believed to be responsible for Type I Myotonic Dystrophy. This lecture will discuss the development of RBDCC, its use as an enabling tool for identifying sequence-selective RNA binders, and the further development of RBDCC-discovered compounds as lead molecules with target-relevant activity in vitro and in vivo. We will particularly focus on the development of compounds able to alter -1 ribosomal frameshifting (recoding) in HIV, thereby inhibiting viral replication. As protein recoding is a widely used regulatory mechanism in viruses, bacteria, and eukaryotes (including humans), this strategy should have broad utility.
About the Speaker:
Prof. Benjamin L. Miller completed his undergraduate studies at Miami University (Ohio), receiving degrees in Chemistry (B.S.), Mathematics (A.B.), and German (A.B.) in 1988. He next moved to Stanford University, where he carried out his Ph. D. research in Chemistry under the direction of Paul Wender. Following a stint as an NIH postdoctoral fellow at Harvard in Stuart Schreiber’s laboratory, he joined the University of Rochester faculty in 1996. His group’s expertise in molecular recognition, combinatorial chemistry, nanotechnology, and optical sensing has been applied to the development of novel optical biosensor platforms and synthetic compounds targeting several human diseases. He is currently Professor of Dermatology, Biochemistry and Biophysics, Biomedical Engineering, and Optics. As an entrepreneur, Miller is a founder of Adarza BioSystems, Inc., a multiplex optical biodetection company located in St. Louis, MO. He is also the Academic Lead for Integrated Photonic Sensors in AIM Photonics.