Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Taipei 115 (Taiwan); Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 300 (Taiwan).
Angew Chem Int Ed Engl. 2014 Feb 24;53(9):2413-6. doi: 10.1002/anie.201309646. Epub 2014 Jan 31.
Human lung epithelial cells natively offer terminal N-acetylneuraminic acid (Neu5Ac) α(2→6)-linked to galactose (Gal) as binding sites for influenza virus hemagglutinin. N-Glycolylneuraminic acid (Neu5Gc) in place of Neu5Ac is known to affect hemagglutinin binding in other species. Not normally generated by humans, Neu5Gc may find its way to human cells from dietary sources. To compare their influence in influenza virus infection, six trisaccharides with Neu5Ac or Neu5Gc α(2→6) linked to Gal and with different reducing end sugar units were prepared using one-pot assembly and divergent transformation. The sugar assembly made use of an N-phthaloyl-protected sialyl imidate for chemoselective activation and α-stereoselective coupling with a thiogalactoside. Assessment of cytopathic effect showed that the Neu5Gc-capped trisaccharides inhibited the viral infection better than their Neu5Ac counterparts.
人肺上皮细胞天然提供末端 N-乙酰神经氨酸（Neu5Ac）α（2→6）与半乳糖（Gal）相连作为流感病毒血凝素的结合位点。已知 N-羟乙酰神经氨酸（Neu5Gc）代替 Neu5Ac 会影响其他物种的血凝素结合。Neu5Gc 通常不会在人体内产生，它可能会从饮食来源进入人体细胞。为了比较它们在流感病毒感染中的影响，使用一锅法组装和发散转化制备了六种具有 Neu5Ac 或 Neu5Gcα（2→6）与 Gal 相连且具有不同还原端糖单位的三糖。糖的组装利用 N-邻苯二甲酰保护的唾液酸亚胺进行化学选择性激活，并与硫代半乳糖苷进行 α-立体选择性偶联。细胞病变效应评估表明，带有 Neu5Gc 的三糖比其 Neu5Ac 对应物更能抑制病毒感染。
