Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia.
J Med Chem. 2012 Oct 25;55(20):8963-8. doi: 10.1021/jm301145k. Epub 2012 Oct 11.
A series of C3 O-functionalized 2-acetamido-2-deoxy-Δ⁴-β-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-μM level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.
为了探究流感病毒神经氨酸酶活性位点中 2 位的非电荷相互作用，我们合成了一系列 C3 位连有 O-取代基的 2-乙酰氨基-2-去氧-Δ⁴-β-D-葡糖醛酸苷。与 A/N8 神经氨酸酶形成复合物时，母体化合物（C3 OH）会发生溶液构象反转，使所有取代基都能在活性位点中很好地定位。母体化合物对流感病毒神经氨酸酶的抑制作用可达到亚微摩尔水平；在 C3 位引入小烷基取代基或乙酰基也是可以接受的。
