The capsular polysaccharide of the meningitis-causing bacteria <i>N. meningitidis</i> serogroup B and <i>E. coli</i> K1 is a linear homopolymer known as α(2-8)-polysialic acid (PolySia). Previous characterizations of PolySia have focused primarily on the structure of the α-linked residues; however no consensus has been reached, with proposals ranging from a variety of helical conformations to random coils. In solution, the reducing-end of free PolySia is found mostly in the β-configuration with the C2’s OH in the axial orientation. A molecular dynamics (MD) study on Siaα(2-8)SiaβOH unexpectedly predicted a well-defined structure for this dimer. We show by MD studies of related compounds that the orientation of the terminal βOH favors the formation of a hydrogen bond between the reducing end OH and the axial carboxylate group of the next residue. Moreover, MD predicts that the two terminal residues at the reducing end of α(2-8)-PolySia constitute a stable structural motif, distinct from the extended polymer structure. All these theoretical predictions are then experimentally supported by a range of NMR experiments, including residual dipolar couplings, long-range correlation experiments, ROEs, and OH/OD exchange studies. We suggest the hypothesis that the reported structural motif sheds light on a longtime puzzling observation for the requirement of 10 residues of α(2–8)-PolySia in order to bind effectively to specific antibodies, about four units more than for analogous cases. We expect these results to open the door to a more accurate description of free PolySia in solution.

Characterization of the distinct sructural motif of α(2-8)-polysialic acid at the reducing end

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.