Frequent Occurrence of Pre-existing α2→8-Linked Disialic and Oligosialic Acids with Chain Lengths Up to 7 Sia Residues in Mammalian Brain Glycoproteins

Abstract

The pre-existence of α2→8-linked disialic acid (di-Sia) and oligosialic acid (oligo-Sia) structures with up to 7 Sia residues was shown to occur on a large number of brain glycoproteins, including neural cell adhesion molecules (N-CAMs), by two highly sensitive chemical methods (Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1998) 261, 191–197; Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1999) . 266, 102–109). This unexpected finding was also confirmed using a newly developed antibody prepared using a copolymer of α2→8-linked -acetylneuraminyl-vinylbenzylamide and acrylamide as an immunogen and known antibodies whose immunospecificities were determined to be di- and oligo-Sia residues with defined chain lengths. The major significance of the new finding that di- and oligo-Sia chains exist on a large number of brain glycoproteins is 2-fold. First, it reveals a surprising diversity in the number and of proteins distinct from N-CAM that are covalently modified by these short sialyl glycotopes. Second, it suggests that synthesis of di- and/or oligo-Sia units may be catalyzed by α2→8-sialyltransferase(s) that are distinct from the known polysialyltransferases, STX and PST, which are partially responsible for polysialylation of N-CAM.