MASS SPECTROMETRY OF DRUGS, NATURAL PRODUCTS, PROTEINS, AND OLIGONUCLEOTIDES

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Research of the unit is split between the identification of biologically active trace organic compounds isolated from natural sources and the mass spectrometry of biopolymers (e.g. peptide, proteins and oligonucleotides). A very close working relationship and collaboration is maintained with the Laboratory of Biophysical Chemistry, NHLBI. While this group runs many routine analyses for laboratories at NIH, as much emphasis as possible is placed on research using mass spectrometry for the structural elucidation of biologically active compounds. This years key projects include: the structural identification of potent anti-HIV and anti-cancer compounds; the identification of post-translational modifications in proteins; continued research on cyanovirin, a potent anti-HIV compound heading towards clinical trial; development of techniques for micro- scale LCMS of biopolymers with the aim of greatly enhancing sensitivity; the identification and chiral determination of abnormal and modified amino acids as found in marine natural products; the identification of modified hemoglobins formed during treatments for sickle cell. Work has expanded into large proteins with multiple glycosylation sites and many overlapping disulfides. Multiple enzymatic digestion protocols and sophisticated software have been developed to solve these problems. A collaboration continues with The National Institute of Standards and Technology (NIST) involving the measurement of mass spectra of organic compounds from NIH, the Walter Reed Army Institute of Research and other government agencies. These are then put into the NIST/EPA/NIH mass spectral database which is in use world wide. - mass spectrometry, proteins, disulfides, glycosylation, electrospray, natural products, anti-HIV, sickle cell anemia