This project uses the methods of physical chemistry to investigate the equilibrium distribution of energetically preferred conformations of carbohydrate polymers and oligomers and the rates and mechanisms by which these molecules pass from one conformation to another. Oligo- and polysaccharides play an important part in the biological processes of cellular recognition, signaling, and adhesion. Bacterial capsular polysaccharides, for example, frequently elicit an immune response in the host organism and, hence, have potential uses in the production of vaccines against pathogenic organisms. The capacity of carbohydrate macromolecules for diversity of structure and conformation makes them ideal candidates for roles in the storage and expression of biological information at the surfaces of biological cells. A full understanding of these processes demands a appreciation of the process by which a particular primary sequence of sugars expresses its conformational preferences, the interactions which stabilize the preferred conformations, and the processes and pathways by which these large molecules pass from one conformation to another among the various molecular shapes in the equilibrium distribution. In this project several structurally simple polymers of glucose are investigated by means of NMR relaxation and dynamic rheology to probe their rates of motion on the nanosecond and microsecond time scales. These experiments are complemented by a theoretical analysis designed to interpret the observable dynamic properties on a molecular basis. Such studies probe the fundamental processes of intramolecular motion that may occur as a carbohydrate ligand interacts with a protein receptor. The structure and stability of multiple-stranded helical structures in two classes of microbial polysaccharides are investigated using such techniques as NMR spectroscopy, electron and scanning probe microscopy, light scattering, scanning calorimetry, and conformational modeling. These studies are designed to elucidate the nature and strength of the solvent- modulated carbohydrate-carbohydrate interactions that determine carbohydrate conformation in aqueous media. Such carbohydrate-carbohydrate interactions may also be involved in certain biological recognition processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033062-15
Application #
2734492
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1983-07-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Chemistry
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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