Chemoenzymatic synthesis of artificial glycopolypeptides containing multivalent sialyloligosaccharides with a γ-polyglutamic acid backbone and their effect on inhibition of infection by influenza viruses
Chemoenzymatic synthesis of artificial glycopolypeptides containing multivalent sialyloligosaccharides with a γ-polyglutamic acid backbone and their effect on inhibition of infection by influenza viruses
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DOI：
10.1016/j.bmc.2006.11.006
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发表时间：
2007-02-01
影响因子：
3.5
通讯作者：
Usui, Taichi
中科院分区：
文献类型：
--
作者：
Ogata, Makoto;Murata, Takeomi;Usui, Taichi
从枯草芽孢杆菌中提取的具有γ-聚谷氨酸(Gamma-PGA)主干的高度水溶性的人工糖多肽。多价唾液酸寡糖单元已被化学酶法合成，作为禽流感病毒和人类流感病毒感染的潜在聚合物抑制剂。以乳糖和乳糖为原料，通过纤维素酶催化与5-三氟乙酰胺-1-戊醇缩合，分别合成了5-三氟乙酰氨基戊基-β-N-乙酰乳糖胺和5-三氟乙酰氨基戊基-β-乳糖苷。脱乙酰基后，得到的5-氨基戊基β-LacNAc和β-内酯糖苷偶联到7-PGA侧链的α-羧基上。携带LacNAc和乳糖的人工糖多肽被α2，3-和α2，6-唾液酸转移酶进一步转化为Neu5Acα2-(3/6)Galβ1-4G1cβ和Neu5Acα2-(3/6)GalP1-4G1cNAcβ唾液酸低聚糖单位。用三种不同的方法研究了这些糖多肽与不同流感病毒株的相互作用。携带Neu5Acα2，6LacNAc的糖多肽抑制甲型和乙型流感病毒介导的血凝，其与血凝素的相对结合亲和力比自然产生的胎球蛋白对照高10(2)~10(4)倍。携带Neu5Aca2，6LacNAc的糖多肽对A/Mapphis/1/71(H3N2)感染的抑制作用是胎球蛋白的93倍。通过对感染病毒的MDCK细胞的细胞病变效应进行评估。禽流感病毒[A/Duck/Hong Kong/4/78(H5N3)]与Neu5Acα2，3LacNAc/Lac糖多肽结合较强，而人病毒[A/Mephis/1/71(H3N2)]与Neu5Acα2.6LacNAc结合优先于Neu5Acα2，6Lac。综上所述，这些结果表明病毒与末端唾液酸的结合明显受到糖多肽糖链中asialo部分的结构的影响，在这种情况下是LacNAc或乳糖。(C)2006爱思唯尔有限公司。保留所有权利。
Highly water-soluble, artificial glycopolypeptides with a gamma-polyglutamic acid (gamma-PGA) backbone derived from Bacillus subtilis sp. and multivalent sialyloligosaccharide units have been chemoenzymatically synthesized as potential polymeric inhibitors of infection by bird and human influenza viruses. 5-Trifluoroacetamidopentyl beta-N-acetyllactosaminide and 5-trifluoroacetamidopentyl beta-lactoside were enzymatically synthesized from LacNAc and lactose, respectively, by cellulase-mediated condensation with 5-trifluoroacetamido-1-pentanol. After deacetylation, the resulting 5-aminopentyl beta-LacNAc and beta-lactoside glycosides were coupled to the alpha-carboxyl groups of the 7-PGA side chains. The artificial glycopolypeptides carrying LacNAc and lactose were further converted to Neu5Ac alpha 2-(3/6)Gal beta 1-4G1c beta and Neu5Ac alpha 2-(3/6)GalP1-4G1cNAc beta sialyloligosaccharide units by alpha 2,3- and alpha 2,6-sialyltransferase, respectively. The interaction of these glycopolypeptides with various influenza virus strains has been investigated by three different methods. Glycopolypeptides carrying Neu5Ac alpha 2,6LacNAc inhibited hemagglutination mediated by influenza A and B viruses, and their relative binding affinities for hemagglutinin were 10(2) to 10(4)-fold higher than that of the naturally occurring fetuin control. A glycopolypeptide carrying Neu5Aca2,6LacNAc inhibited infection by A/Memphis/1/71 (H3N2) 93 times more strongly than fetuin. as assessed by cytopathic effects on virus-infected MDCK cells. The avian virus [A/duck/Hong kong/4/78 (H5N3)] bound strongly to Neu5Ac alpha 2,3LacNAc/Lac-carrying glycopolypeptides, whereas the human virus [A/Memphis/1/71 (H3N2)] bound to Neu5Ac alpha 2.6LacNAc in preference to Neu5Ac alpha 2,6Lac. Taken together, these results indicate that the binding of viruses to terminal sialic acids is markedly affected by the structure of the asialo portion, in this case either LacNAc or lactose, in the sugar chain of glycopolypeptides. (c) 2006 Elsevier Ltd. All rights reserved.