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FTICR Mass Spectrometry: A New Paradigm for Discovery Against RNA Targets

presented by

Richard Griffey
Isis Pharmaceuticals

July 30, 1998

The Scripps Research Institute, W.M. Keck Foundation Amphitheater


Background:

Richard H. Griffey has been involved in mass spectrometry for some twenty years. Beginning with his undergraduate study in Chemistry at Rice University, he researched mass spectroscopy of strained cyclic organic molecules. Rich then obtained a Ph.D. in Organic Chemistry at the University of Utah, focusing his research there on the synthesis and incorporation of stable isotope labels into nucleic acids and also on the development of new NMR techniques. As an NIH Postdoctoral Fellow at Brandeis University, Dr. Griffey concentrated on research on the structure of proteins and nucleic acids using stable isotope-enriched biomolecules and high field NMR under Professor A.G. Redfield. Rich spent the next six years at the University of New Mexico School of Medicine, working first as a professor in the Dept. of Cell Biology and later as the Director of Biomedical Spectroscopy. He has been at Isis Pharmaceuticals for the past seven years, working in various capacities in several different chemistry departments and is now the Senior Director of Combinatorial Drug Discovery.

Abstract:

The application of mass spectrometry in the screening of small molecule libraries against RNA targets is described. Mass spectrometry offers several advantages for characterization of hits compared to conventional HTS protocols, including direct compound identification based on exact molecular mass, measurement of binding constants, and location of binding sites. In MS-based screening approaches, mixtures of compounds can be screened simultaneously against multiple RNA targets in a massively parallel strategy. These advantages are demonstrated for characterization of compounds that bind to a model of the 16S A site of the small ribosomal subunit of E. coli.

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