The goal of this project is to determine the structure of bacterial capsular polysaccharides related to invasive disease in humans and to characterize the conformation of these bacterial polysaccharides through NMR studies and theoretical calculations. The binding to antibodies against the polysaccharides and the structure of the bound antigen are also to be determined. The conformational preference of disaccharides have been studied by NOE NMR methods and are currently being compared to molecular dynamics trajectories that have been generated under a variety of conditions (e.g., solvent dielectric, differing force fields). Theoretical NOE build-up curves have been constructed from these simulations assuming that conformational interconversion is slow relative to overall tumbling; methods to calculate expected NOEs assuming rapid internal motions are being developed. Extensive NMR relaxation time studies (T1, T2, NOE at differing magnetic field strengths) of various size distributions of the Group B meningococal capsular polysaccharides (2-8 linked sialic acid) have been carried out and are currently being fitted to various motional dynamics models. It is already apparent that the relaxation data is not accommodated by models of rigid isotropic or rigid anisotropic motion. Models incorporating internal motions are now being pursued. The binding of oligosaccharides of the Group B polymer to various monoclonal antibodies are now being studied using capillary electrophoresis.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BI004005-01
Application #
3770268
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost