Molecular Design of Glycopolymers Having Biological Recongnition Function via Glycosidation

流感病毒膜上的血凝素糖蛋白(HA)负责在感染过程中与细胞表面受体结合，已知唾液乳糖与流感病毒HA结合。我们用从牛乳中分离的α(2-3)和α(2-6)连接的异构体唾液酸乳糖(摩尔比为6.5：1)的混合物，通过一种简便的步骤合成了携带唾液乳糖的糖共聚物。用血凝抑制法研究了含唾液酸乳糖的糖共聚物与病毒的相互作用。这些糖共轭聚合物比相应的糖本身更能抑制病毒的血凝活性。本文提出了一种简便的一步法合成唾液酸单糖和唾液二糖取代的苯乙烯类化合物的方法。N-乙酰神经氨酸(Neu5Ac)和唾液二糖(Neu5Acalpha2-8Neu5Ac)在酰胺化试剂存在下与对乙烯基苄胺反应，得到的苯乙烯衍生物在氧化还原引发剂存在下与丙烯酰胺均聚并共聚。聚合物与WGA的相互作用比相应的单体更强。聚合物中糖的摩尔分数对WGA凝集素的识别有影响。含唾液酸单糖的共聚物结合能力最强(共聚物中糖的摩尔分数为0.32)。含唾液酸单糖的共聚物(共聚物中糖的摩尔分数为0.13)在0.02 mM浓度下表现出血凝活性。

The hemagglutinin glycoprotein (HA) of the influenza virus membrane is responsible for binding the cell surface receptors during infection, ant sialyllactose is known to bind to the influenza HA.We synthesized sialyllactose-carrying glycopolymers via a convenient procedure using a mixture of alpha(2-3) and alpha(2-6)-linked isomeric sialyllactose (the molar ratio, 6.5 : 1) isolated from bovine milk. The interaction of sialyllactose-carrying glycopolymers with virus was investigated by means of inhibition of hemagglutination. These glycoconjugate polymers inhibited hemagglutinating activity of virus more strongly than the corresponding sugar itself. The inhibition with sialyllactose-carrying homopolymer was about 1*10^3 times that with silalyllactose.A convenient one-step synthetic method is proposed to prepare stirene derivatives substituted with sialomono- and sialodisaccharides. N-Acetylneuraminic acid (Neu5Ac) and sialodisaccharide (Neu5Acalpha2-8Neu5Ac) were treated with p-vinylbenzylamine in the presence of amidation reagents and the resulting stirene derivatives were homo- and copolymerized with acrylamide in the presence of redox initiator. The polymers interacted with WGA lecting more strongly than the corresponding monomer. Mol fraction of sugars in polymer had influence on the recognition of WGA lectin. THe strongest binding was observed for the copolymer bearing sialomonosaccharide (mol fraction of sugar in copolymer : 0.32). The copolymer bearing sialomonosaccharide (mol fraction of sugar in copolymer : 0.13) showed hemagglutinating activity at 0.02mM concentration..