Differential Reactivity of Two Types of N-Glycolylneuraminic Acid Dimers toward Enzymatic and Nonenzymatic Hydrolysis of Their Interketosidic Linkages

Abstract

The kinetics of acid- and sialidase-catalyzed hydrolysis of the interketosidic linkages of two different disialic acids, Neu5Gcα2→5-OglycolylNeu5Gc and Neu5Gcα2→8Neu5Gc, were studied. The former sequence was recently identified in the polysialic acid chains of a sialic acid-rich glycoprotein isolated from the egg jelly coat of two different species of sea urchins, and the latter was previously found in the cortical alveolar-derived polysialoglycoprotein from rainbow trout eggs. At pH values < 3.8, the rate of hydrolysis of Neu5Gcα2→5-OglycolylNeu5Gc was greater than that of Neu5Gcα2→8Neu5Gc. Paradoxically, however, Neu5Gcα2→5-OglycolylNeu5Gc was more stable than Neu5Gcα2→8Neu5Gc at pH values > 3.8. These findings indicate a greater contribution of intramolecular general acid catalysis to the lability of the α2→5-ketosidic linkage. Neu5Gcα2→5-OglycolylNeu5Gc was a poor substrate for Arthrobacter ureafaciens, Clostridium perfringens, and Vibrio cholerae sialidases, in contrast to Neu5Gcα2→8Neu5Gc. Neu5Gcα2→5-OglycolylNeu5Gc was essentially resistant to hydrolysis by A. ureafaciens sialidase.