新型 3,4-二取代 Neu5Ac2en 衍生物作为探针研究流感病毒神经氨酸酶 150 环的柔性。

Novel 3,4-disubstituted-Neu5Ac2en derivatives as probes to investigate flexibility of the influenza virus sialidase 150-loop.

机构信息

Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.

出版信息

Bioorg Med Chem. 2013 Aug 15;21(16):4820-30. doi: 10.1016/j.bmc.2013.05.054. Epub 2013 Jun 6.

DOI:10.1016/j.bmc.2013.05.054

Abstract

Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.

摘要

新型 3,4-二取代-Neu5Ac2en 衍生物被合成以探测流感病毒神经氨酸酶的开放 150 环构象。通过 4-表位-羟基衍生物，制备了赤道位和轴向（表位）取代的 C4 氨基和胍基 3-（对甲苯基）烯丙基-Neu5Ac2en 衍生物。赤道位取代的 4-氨基衍生物对组 1（pdm09 H1N1）和组 2（pdm57 H2N2）神经氨酸酶均表现出低微摩尔抑制作用，这首次提供了体外证据表明组 2 神经氨酸酶可能表现出 150 环灵活性。