We propose to acquire a MALDI TOF/TOF mass spectrometer, which will provide crucial support for health-related research at UW-Madison. Specific research projects that will benefit include: 1) the design of unnatural oligomers (foldamers) to block disease-associated protein-protein interactions; 2) the development of biomaterials that function as tissue engineering substrates or coatings for implanted orthopedic medical devices; 3) the identification of neuropeptides in the nematode, a simple model for nervous system function; 4) the design of small molecules that disrupt bacterial quorum sensing, which can serve as tools for basic biological research and as leads to new antibacterial agents; 5) the mapping of relationships between polyphenols (tannins) found in fruits and other foods and bioactivity in cell culture and in vitro models of inflammation, bacterial adherence and oxidation; 6) the elucidation of protein folding that occurs concomitantly with ribosomal biosynthesis; 7) the design of new polymers that mimic the selective antimicrobial activity of host-defense peptides. The proposed instrument will be a crucial addition to the MS facility in the UW Chemistry Department because it will allow routine structure determination via fragmentation (e.g., sequencing of peptides, peptide analogues and polymers). The Chemistry MS facility is unique on the UW campus in allowing 24-hour access to students and other researchers, which is essential for rapid progress in the projects described above. Therefore, the capabilities provided by the requested instrument would constitute an important addition to the scientific infrastructure at a major US research institution. ? ? ?
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