Our aim, in this proposal, is to continue our research efforts to chemically and structurally characterize purified human tracheobronchial glycoproteins. Primary emphasis is placed on analyzing the major sulfated oligosaccharides and the major oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. The focus of this proposal stresses the characterization of the sulfated oligosaccharides since it is primarily this fraction that increases with severity of a lung disease. Tracheobronchial glycoproteins and isolated fractions from patients suffering from various forms of chronic obstructive pulmonary disease (e.g., chronic bronchitis, asthma, bronchiectasis, alveolar proteinosis and cystic fibrosis (CF)) will be studied, their structures elucidated and compared so as to gain insight from different pathological vectors on how the tracheobronchial submusocal glands alter their secretory glycoprotein structure in response to chronic disease. Since the start of the initial proposal, we have made substantial and significant progress in elucidating the structures of many sulfated oligosaccharides. We propose to continue this exciting work, in addition to enhancing our research efforts in analyzing the different oligosaccharide-oligopeptide fractions isolated from tracheobronchial glycoproteins. Gas-liquid chromatography and mass spectrometry will be employed in all chemical investigations which will also include several new analytical techniques developed during the initial proposal period for the analysis of amino and neutral sugars, amino acids and carboxylates. Our knowledge of the structure and related functions of tracheobronchial glycoproteins is still very poor. Over the past two years we have made significant findings; discovering several new sulfated structures. We are gradually beginning to unravel the basic structure of these complex, large molecular weight glycoproteins. Continuation of this research is important so that we can understand the structure/function biochemistry of these very important molecules in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032026-07
Application #
3343228
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1984-06-01
Project End
1992-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Mawhinney, T P; Landrum, D C; Gayer, D A et al. (1992) Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis. Carbohydr Res 235:179-97
Mawhinney, T P; Adelstein, E; Gayer, D A et al. (1992) Structural analysis of monosulfated side-chain oligosaccharides isolated from human tracheobronchial mucous glycoproteins. Carbohydr Res 223:187-207
Christensen, G D; Barker, L P; Mawhinney, T P et al. (1990) Identification of an antigenic marker of slime production for Staphylococcus epidermidis. Infect Immun 58:2906-11
Landrum, D C; Mawhinney, T P (1989) Gas-liquid chromatography-mass spectrometry of mono- and dithiols as their tert.-butyldimethylsilyl derivatives. J Chromatogr 483:21-32
Mawhinney, T P; Adelstein, E; Morris, D A et al. (1987) Structure determination of five sulfated oligosaccharides derived from tracheobronchial mucus glycoproteins. J Biol Chem 262:2994-3001
Mawhinney, T P; Robinett, R S; Atalay, A et al. (1986) Gas-liquid chromatography and mass spectral analysis of mono-, di- and tricarboxylates as their tert.-butyldimethylsilyl derivatives. J Chromatogr 361:117-30
Mawhinney, T P (1986) Simultaneous determination of N-acetylglucosamine, N-acetylgalactosamine, N-acetylglucosaminitol and N-acetylgalactosaminitol by gas-liquid chromatography. J Chromatogr 351:91-102
Mawhinney, T P; Robinett, R S; Atalay, A et al. (1986) Analysis of amino acids as their tert.-butyldimethylsilyl derivatives by gas-liquid chromatography and mass spectrometry. J Chromatogr 358:231-42