This project is designed to explore fundamental relationships between the chemical structure and the molecular conformation and dynamics of carbohydrate macromolecules. These widely distributed compounds are essential structural and energy storage components of all living systems. Their function is increasingly recognized at eukaryotic cell surfaces where, by virtue of their capacity for topological and conformational diversity, they are responsible for the storage and expression of biological information that governs such phenomena as blood type, regulation of the blood coagulation chain, allograft acceptance or rejection, growth factor reception and regulation, and cell-cell recognition and adhesion. Bacterial capsular polysaccharides function in these organisms as a protective shell and govern the activity of water at the external cell surface and the adhesive properties of the cell. This extracellular polysaccharide contains an antigenic determinant in many pathogenic bacteria, and cell-free samples are used as vaccines. The question of chemical structure and macromolecular conformation is approached using a combination of computer modeling and quantitative experimental characterization of the dilute solution properties. Because the emphasis is on high polymers, which necessarily exhibit conformational variability even when they adopt relatively ordered helical conformations, the methods of statistical mechanics must be used in the computer modeling to make a quantitative and conceptually accurate connection between chemical structure and observable physical properties. Observable characteristics of interest are those computed with fewest approximations from the statistical theory. Emphasis is on global conformational features obtainable from light scattering and hydrodynamic measurements and on local conformational features accessible from appropriate NMR measurements. Dynamic as well as equilibrium properties of these systems are under investigation. 13C NMR relaxation measurements are used to probe the frequency spectrum of conformational motions, and these observations are interpreted in detailed molecular terms using realistic computer simulations of the molecular dynamics of aqueous oligosaccharides.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM033062-07A1
Application #
3282415
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1983-07-01
Project End
1995-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
McIntire, Theresa M; Lew, Ellen J L; Adalsteins, A Elva et al. (2005) Atomic force microscopy of a hybrid high-molecular-weight glutenin subunit from a transgenic hexaploid wheat. Biopolymers 78:53-61
Jaud, Simon; Tobias, Douglas J; Brant, David A (2005) Molecular dynamics simulations of aqueous pullulan oligomers. Biomacromolecules 6:1239-51
Lee, Hu-Cheng; Brant, David A (2002) Rheology of concentrated isotropic and anisotropic xanthan solutions: 3. Temperature dependence. Biomacromolecules 3:742-53
McIntire, T M; Brant, D A (1999) Imaging of carrageenan macrocycles and amylose using noncontact atomic force microscopy. Int J Biol Macromol 26:303-10
Brant, D A (1999) Novel approaches to the analysis of polysaccharide structures. Curr Opin Struct Biol 9:556-62
Brant, D A; Liu, H S; Zhu, Z S (1995) The dependence of glucan conformational dynamics on linkage position and stereochemistry. Carbohydr Res 278:11-26
Oviatt Jr, H W; Brant, D A (1993) Thermal treatment of semi-dilute aqueous xanthan solutions yields weak gels with properties resembling hyaluronic acid. Int J Biol Macromol 15:3-10
Stokke, B T; Elgsaeter, A; Brant, D A et al. (1993) Macromolecular cyclization of (1-->6)-branched-(1-->3)-beta-D-glucans observed after denaturation-renaturation of the triple-helical structure. Biopolymers 33:193-8
Kadkhodaei, M; Wu, H; Brant, D A (1991) Comparison of the conformational dynamics of the (1----4)- and (1----6)-linked alpha-D-glucans using 13C-NMR relaxation. Biopolymers 31:1581-92
Stokke, B T; Brant, D A (1990) The reliability of wormlike polysaccharide chain dimensions estimated from electron micrographs. Biopolymers 30:1161-81

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