N-酰基和N-卤乙酰神经氨酸的生物学特性：经唾液酸代谢酶的加工处理以及与流感病毒的相互作用

Biological properties of N-acyl and N-haloacetyl neuraminic acids: processing by enzymes of sialic acid metabolism, and interaction with influenza virus.

作者信息

Humphrey Andrew J, Fremann Claire, Critchley Peter, Malykh Yanina, Schauer Roland, Bugg Timothy D H

机构信息

Department of Chemistry, University of Southampton, Highfield, Southampton, UK.

出版信息

Bioorg Med Chem. 2002 Oct;10(10):3175-85. doi: 10.1016/s0968-0896(02)00213-4.

DOI:10.1016/s0968-0896(02)00213-4

PMID:12150863

Abstract

Several unnatural N-acyl neuraminic acids (N-propionyl, N-hexanoyl, N-benzoyl, N-trifluoroacetyl, N-chloroacetyl, N-difluoroacetyl) were prepared enzymatically using immobilised sialic acid aldolase. N-Trifluoroacetyl-, N-chloroacetyl- and N-difluoroacetyl neuraminic acids were shown to enhance up to 10-fold the rate of association of influenza virus A to a sialoglycolipid neomembrane by surface plasmon resonance, and were found to act as weak inhibitors (K(iapp) 0.45-2.0 mM) of influenza virus neuraminidase. The N-propionyl, N-chloroacetyl- and N-difluoroacetyl neuraminic acids were found to be substrates for recombinant Escherichia coli CMP sialate synthase, to give the corresponding CMP-N-acyl-neuraminic acids. CMP-N-propionyl neuraminic acid was found not to be a substrate for CMP-N-acetyl neuraminic acid hydroxylase from pig submandibular gland.

摘要

使用固定化唾液酸醛缩酶酶法制备了几种非天然的N-酰基神经氨酸（N-丙酰基、N-己酰基、N-苯甲酰基、N-三氟乙酰基、N-氯乙酰基、N-二氟乙酰基）。通过表面等离子体共振显示，N-三氟乙酰基、N-氯乙酰基和N-二氟乙酰基神经氨酸可将甲型流感病毒与唾液糖脂新膜的结合速率提高多达10倍，并且发现它们可作为流感病毒神经氨酸酶的弱抑制剂（表观抑制常数K(iapp)为0.45 - 2.0 mM）。发现N-丙酰基、N-氯乙酰基和N-二氟乙酰基神经氨酸是重组大肠杆菌CMP唾液酸合酶合成相应CMP-N-酰基神经氨酸的底物。发现CMP-N-丙酰基神经氨酸不是猪下颌下腺CMP-N-乙酰神经氨酸羟化酶的底物。