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

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK032102-03
Application #
6289766
Study Section
Special Emphasis Panel (LBC)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Hess, Sonja; van Beek, Jacco; Pannell, Lewis K (2002) Acid hydrolysis of silk fibroins and determination of the enrichment of isotopically labeled amino acids using precolumn derivatization and high-performance liquid chromatography-electrospray ionization-mass spectrometry. Anal Biochem 311:19-26
Gladwin, Mark T; Shelhamer, James H; Ognibene, Frederick P et al. (2002) Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease. Br J Haematol 116:436-44
Rashid, M A; Gustafson, K R; Cartner, L K et al. (2001) Microspinosamide, a new HIV-inhibitory cyclic depsipeptide from the marine sponge Sidonops microspinosa. J Nat Prod 64:117-21
Bokesch, H R; Pannell, L K; Cochran, P K et al. (2001) A novel anti-HIV macrocyclic peptide from Palicourea condensata. J Nat Prod 64:249-50
Li, Y F; Hess, S; Pannell, L K et al. (2001) In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 98:10578-83
Orsini, M A; Pannell, L K; Erickson, K L (2001) Polychlorinated acetamides from the cyanobacterium Microcoleus lyngbyaceus. J Nat Prod 64:572-7
Manfredi, K P; Vallurupalli, V; Demidova, M et al. (2001) Isolation of an anti-HIV diprenylated bibenzyl from Glycyrrhiza lepidota. Phytochemistry 58:153-7
Gustafson, K R; Walton, L K; Sowder Jr, R C et al. (2000) New circulin macrocyclic polypeptides from Chassalia parvifolia. J Nat Prod 63:176-8
Rashid, M A; Gustafson, K R; Boswell, J L et al. (2000) Haligramides A and B, two new cytotoxic hexapeptides from the marine sponge Haliclona nigra. J Nat Prod 63:956-9
Driscoll, W J; Konig, S; Fales, H M et al. (2000) Peptidylglycine-alpha-hydroxylating monooxygenase generates two hydroxylated products from its mechanism-based suicide substrate, 4-phenyl-3-butenoic acid. Biochemistry 39:8007-16

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