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

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Specialized mass spectrometric analyses are provided to the institute and to other collaborating units. The emphasis 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. 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 of Perilipin C which mediates lipid metabolism; an examination of sialic acid in relation to malaria transmission by mosquitos; 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 anaemia; sequence corrections to the hemoglobin alpha- and beta-chains of the rhesus monkey used in sickle cell research; and the development of methods for phospholipid identification. The addition of a new HP-LCMS instrument late last year has drastically expanded the abilities and productivity of the group. 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.