Purchase of a MALDI-TOF Mass Spectrometer

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The goal of this proposal is to purchase a MALDI-TOF mass spectrometer to enhance ongoing research programs at Wayne State University in the areas of A) modified nucleic-acid structure (naturally modified RNAs, DNA-carcinogen adducts, platinated DNAs, DNAs with non-natural base modifications), B) protein structure and interactions (novel metalloproteins, phosphorylated and post- translationally modified proteins, DNA polyrnerases, and antibodies), and C) glycopeptide chemistry (alpha-Gal epitope mimetic libraries). These topics represent the research areas of five established NIH- funded laboratories in the Departments of Chemistry and Pharmacology. At least 75% of the instrument time will be devoted to these projects. The remaining 25% of instrument time will be devoted to other active research areas at Wayne State, including the study of A) PDZ protein domains and B) organic dendrimers. A central, shared MALDI-TOF mass spectrometer is currently not available at Wayne State. This important analytical tool is very much needed by the applicants in order to carry out routine characterization of biomolecules (RNAs, DNAs, carbohydrates, and proteins), polymers, and synthetic natural products in a manner that is facile, accurate, and requires little material. The addition of MALDI-TOF/MS will greatly enhance our ability to analyze these molecules with high throughput. Due to the increasingly large number of groups at Wayne State performing studies on macromolecules, including several recent hires in the areas of bioorganic and bioinorganic chemistry, our demands have far exceeded the capabilities of the current LC/MS instrument. The addition of MALDI-TOF will allow for more optimal use of the current LC/MS instrument and the two instruments would therefore have complementary roles. The requested MALDI-TOF instrument will be housed in the Chemistry Department in the Central Instrument Facility (CIF) at Wayne State. The facility has both internal and external funding support, assuring that the instrument will be properly maintained and operated at the most efficient level. The CIF provides Ph.D.-level expertise in mass spectral techniques, and several in-house experts on mass spectrometry and MALDI-TOF will play key advisory roles.