We designed a series of gamma-polyglutamic acid (gamma-PGA)-based glycopolypeptides carrying long/short alpha2,3/6 sialylated glycans to act inhibitors of the influenza virus. As an alternative design, sialoglycopolypeptides carrying long-spacer linked glycans were engineered by replacement of the N-acetyllactosamine (LN) unit by an alkyl chain. The structure-activity relationship of the resulting sialoglycopolypeptides with different glycans in the array has been investigated by in vitro and in vivo infection experiments. The avian viruses specifically bound to glycopolypeptides carrying a short sialoglycan with higher affinity than to a long glycan. In contrast, human viruses, preferentially bound not only to long alpha2,3/6 sialylated glycan with LN repeats in the receptors, but also to more spacer-linked glycan in which the inner sugar has been replaced by a nonsugar structural unit such as a pentylamido group. Taken together, our results indicate that a spaced tandem/triplet pentylamido repeat is a good mimetic of a tandem/triplet LN repeat. Our strategy provides a facile way to design strong polymeric inhibitors of infection by avian and human influenza viruses.
Chemoenzymatic synthesis of sialoglycopolypeptides as glycomimetics to block infection by avian and human influenza viruses
[Category] 조류인플루엔자,
Pubmed URL [DOI] 10.1021/bc800460p
[Source] pubmed
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