Transfer of synthetic sialic acid analogs to N- and O-linked glycoprotein glycans using four different mammalian sialyltransferases

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Abstract
This paper presents kinetic properties of the transfer of several synthetic 9-substituted sialic acid analogues onto N- or O-linked glycoprotein glycans by four purified mammalian sialyltransferases: Gal.beta.1,4GlcNAc .alpha.2,6sialyltransferase, Gal.beta.1,4(3)GlcNac .alpha.2,3sialyltransferase, Ga1.beta.1,3GalNAc .alpha.2,3sialyltransferase, and GalNAc .alpha.2,6sialyltransferase. The substituents at C-9 of the sialic acid analogues introduce special biochemical characteristics: 9-Amino-NeuAc represents, up to the present, the first derivative that is resistant toward bacterial, viral, and mammalian sialidases but is transferred by a sialyltransferase. 9-Acetamido-NeuAc, 9-benzamido-NeuAc, and 9-hexanoylamido-NeuAc differ in size and hydrophobic character from each other and from parent NeuAc. 9-Azido-NeuAc may be used to introduce a photoreactive label. The kinetic properties of the four sialyltransferases with regard to the donor CMP-glycosides differed distinctly depending on the structure of the substituent at C-9. CMP-9-amino-NeuAc was only accepted as donor substrate by Gal.beta.1,4GlcNAc .alpha.2,6sialyltransferase (rat liver), but the Km value was 14-fold higher than that of parent CMP-NeuAc. In contrast, 9-azido-NeuAc was readily transferred by each of these four enzymes. 9-Acetamido-NeuAc, which is a receptor analogue for influenza C virus, 9-benzamido-NeuAc, and 9-hexanoylamido-NeuAc were also accepted by each sialyltransferase, but incorporation values differed significantly depending on the enzyme used. For the first time, the resialylation of asialo-.alpha.1-acid glycoprotein with 9-substituted sialic acid analogues by Gal.beta.1,4GlcNAc .alpha.2,6sialyltransferase is demonstrated.

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