The purpose of this research is to advance knowledge concerning the principles which govern the three dimensional conformations of glycoproteins and to relate molecular shape to biological function by methods similar to those which have been used for polypeptides, proteins and polynucleotides. The conformations of glycoproteins will be determined with special emphasis on their oligosaccharide moieties and their glycopeptide linkage. As conformational models for mucin glycoproteins, the research will use the antifreeze glycoprotein of polar fish as well as blood group A, B, H and Lewis active structures isolated from ovarian cyst mucins. The latter materials include oligosaccharide alditols, glycopeptides and a high molecular weight polysaccharide with blood group A active side chains attached to a polylactosamine backbone. Proton NMR spectra, including proton nuclear Overhauser enhancements (n.O.e.) for the model compounds will be interpreted with the help of conformational energy calculations with empirical potential functions. NMR coupling constants and n.O.e. will be calculated from the coordinates of the low energy molecular conformations for comparison with experimental data. Evidence for internal motion and molecular flexibility will be sought for oligosaccharides with 1-6 linkages by experiments on the temperature dependence of the conformation and by NMR relaxation methods. Conformational calculations for flexible molecules having no single low energy conformation will use statistical Monte Carlo methods. The contributions on non-bonded, electrostatic and solvophobic interactions to the molecular forces responsible for the observed conformations will be determined by experimental measurements of the conformation in nonaqueous solvents and by computational methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031449-10
Application #
3279438
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1989-12-01
Project End
1994-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Maryland Balt CO Campus
Department
Type
Schools of Arts and Sciences
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21250
Xu, Q; Gitti, R; Bush, C A (1996) Comparison of NMR and molecular modeling results for a rigid and a flexible oligosaccharide. Glycobiology 6:281-8
Xu, Q; Mohan, S; Bush, C A (1996) A flexible model for the cell wall polysaccharide of Streptococcus mitis J22 determined by three-dimensional 13C edited nuclear overhauser effect spectroscopy and 13C-1H long-range coupling constants combined with molecular modeling. Biopolymers 38:339-53
Bush, C A (1994) Computer simulations of nuclear Overhauser effect spectra of complex oligosaccharides. Methods Enzymol 240:446-59
Gitti, R; Long, G; Bush, C A (1994) Measurement of long-range2 13C-1H coupling constants of 95% uniformly 13C-labeled polysaccharide from Streptococcus mitis J22. Biopolymers 34:1327-38
Mukhopadhyay, C; Miller, K E; Bush, C A (1994) Conformation of the oligosaccharide receptor for E-selectin. Biopolymers 34:21-9
Mukhopadhyay, C; Bush, C A (1994) Molecular dynamics simulation of oligosaccharides containing N-acetyl neuraminic acid. Biopolymers 34:11-20
Cagas, P; Bush, C A (1992) Conformations of type 1 and type 2 oligosaccharides from ovarian cyst glycoprotein by nuclear Overhauser effect spectroscopy and T1 simulations. Biopolymers 32:277-92
Miller, K E; Mukhopadhyay, C; Cagas, P et al. (1992) Solution structure of the Lewis x oligosaccharide determined by NMR spectroscopy and molecular dynamics simulations. Biochemistry 31:6703-9
Reddy, G P; Bush, C A (1991) High-performance anion exchange-chromatography of neutral milk oligosaccharides and oligosaccharide alditols derived from mucin glycoproteins. Anal Biochem 198:278-84
Mukhopadhyay, C; Bush, C A (1991) Molecular dynamics simulation of Lewis blood groups and related oligosaccharides. Biopolymers 31:1737-46

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