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 uni que extended helical segment (n is similar to 9) of the polymer. The c ritical importance of the carboxylate group to the stability of the ex tended helical epitope can be ascertained from NMR spectrocopic studie s 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 an d 3. This result is also consistent with the fact that the reduced alp ha(2-->8) polysialic acid, contrary to its acidic counterpart, exhibit s conventional immunological properties. Only five to six reduced olig omers are required to inhibit the binding of the reduced polysialic ac id to its homologous antiserum. NMR spectroscopic analysis and potenti al energy calculations on the N-propionyl, N-butanoyl, N-isobutanoyl, N-pentanoyl, N-hexanoyl, and N-glycolyl derivatives of alpha(2-->8) po lysialic acid indicate that, despite the bulk of some of these substit uents, they did not disrupt the extended helical conformer. The presen ce of the extended helical epitope in some of these N-acyl derivatives has also been confirmed from immunological data.