COMPARISON OF THE CONFORMATION OF THE EPITOPE OF ALPHA(2-]8) POLYSIALIC ACID WITH ITS REDUCED AND N-ACYL DERIVATIVES

The immunological properties of alpha(2-->8) polysialic acid have been rationalized in terms of the presence of an epitope situated on a unique extended helical segment (n is similar to 9) of the polymer. The critical importance of the carboxylate group to the stability of the extended helical epitope can be ascertained from NMR spectrocopic studies and potential energy calculations on the carboxyl reduced alpha(2-->8) polysialic acid. These studies indicate that the extended helix (n is similar to 9) is not stabilized in the reduced polymer and that the majority of conformers can only have helical parameters with n = 2 and 3. This result is also consistent with the fact that the reduced alpha(2-->8) polysialic acid, contrary to its acidic counterpart, exhibits conventional immunological properties. Only five to six reduced oligomers are required to inhibit the binding of the reduced polysialic acid to its homologous antiserum. NMR spectroscopic analysis and potential energy calculations on the N-propionyl, N-butanoyl, N-isobutanoyl, N-pentanoyl, N-hexanoyl, and N-glycolyl derivatives of alpha(2-->8) polysialic acid indicate that, despite the bulk of some of these substituents, they did not disrupt the extended helical conformer. The presence of the extended helical epitope in some of these N-acyl derivatives has also been confirmed from immunological data.