sialic acid analogues
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Abstract We present kinetic studies on the enzymatic transfer of several synthetic sialic acid analogues, modified at C-5, to distinct glycoprotein glycans by sialytransferases differing in acceptor- and linkage-specificity. Biochemical properties of sialic acids were modified by introducing formyl-, trifluoroacetyl-, benzyloxycarbonyl-, and aminoacetyl-groups to the amino group at C-5 of neuraminic acid. The latter substitution renders the corresponding α-glyocoside resistant towards sialidases. The respective CMP-sialic acid analogues were prepared by CMP-sialic acid synthase with a yield of 13–55%. The kinetic parameters of several sialyltransferases for the 5-substituted CMP-glycosides differed significantly. Relative to parent CMP-NeuAc, reaction rates of human- and rat liver Galβ1, 4GlcNAc α2,6-sialyl-transferases ranged from 50 to 170%, of GalNAc α2,6-sialyltransferases from 40–140%, and of Galβ1,3Gal-NAc α2,3-sialyltransferase from 20–50%. Resialylation of asialo-α1-acid glycoprotein by 5-N-formyl- and 5-N-aminoacetyl-neuraminic acid employing rat liver Galβ1,4GlcNAc α2,6-sialyltransferase proceeded to about 80% of galactose sites which is identical to the extent achieved with parent NeuAc. According to our data, neosialoglycoconjugates which carry sialic acids modified at theN-acetyl group can be prepared for structure-function analysis, as this position seems crucial for recognition of adhesion proteins and influenza viruses.
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