Syntheses of C‐3‐Modified Sialylglycosides as Selective Inhibitors of Influenza Hemagglutinin and Neuraminidase
Syntheses of C‐3‐Modified Sialylglycosides as Selective Inhibitors of Influenza Hemagglutinin and Neuraminidase
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作为流感血凝素和神经氨酸酶选择性抑制剂的 C-3-修饰唾液酸糖苷的合成
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Chi‐Huey Wong
中科院分区：
文献类型：
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作者：
Xue;Y. Kanie;Chao;Osamu Kanie;Yasuo Suzuki;Chi‐Huey Wong
为了开发作为流感病毒蛋白血凝素和神经氨酸酶抑制剂的新结构，合成了一系列唾液酸衍生物，包括C-3位的一个氢原子被OH或F取代的那些。首先通过一种新的方法合成了具有3-eq-OH基团的唾液酸衍生物，并将其用作C-3位进一步衍生化的关键中间体。研究了这些化合物在酸和唾液酸酶催化水解条件下的稳定性，结果表明，这些化合物对酸和唾液酸酶催化水解条件的耐受性均比它们的母体对硝基苯基α-唾液酸糖苷强。进一步的抑制测定表明，3-ax-OH或F衍生物4、5和24（4的4-差向异构体）是来自产气荚膜梭菌的唾液酸酶以及其他测试的细菌唾液酸酶的有效特异性抑制剂。然而，3-eq-OH衍生物3显示出很小的抑制作用。对人流感唾液酸酶N1和N2的抑制也观察到相同的趋势。化合物3 - 5和唾液酸随后转化为二硬脂酰磷脂酰乙醇胺缀合物。在这些脂质体样化合物中，来自4和5的脂质体样化合物显示出对血凝素H3亚型的有效和选择性抑制活性，但显示出对流感病毒神经氨酸酶N1和N2的抗性。
In an effort to develop new structures as inhibitors of both influenza virus proteins hemagglutinin and neuraminidase, a series of sialic acid derivatives, including those with one of the hydrogen atoms at the C-3 position replaced by either OH or F, were synthesized. The sialic acid derivative with a 3-eq-OH group was first synthesized by means of a new process and used as the key intermediate for further derivatization at the C-3 position. The stability of these compounds under acid- and sialidase-catalyzed hydrolysis conditions was studied, and the results showed that these compounds exhibit stronger resistance towards both conditions than their parent p-nitrophenyl α-sialoside. Further inhibition assay indicated that the 3-ax-OH or F derivatives 4, 5, and 24, the 4-epimer of 4, are effective specific inhibitors of the sialidases from Clostridium perfringens, among other bacterial sialidases tested. The 3-eq-OH derivative 3, however, showed little inhibition. The same tendency was observed for the inhibition of human influenza sialidases N1 and N2. Compounds 3−5 and sialic acid were then converted into the distealoylphosphatidylethanolamine conjugates. Of these liposome-like compounds, the ones from 4 and 5 showed potent and selective inhibitory activities against the hemagglutinin H3 subtype, but displayed resistance to the influenza virus neuraminidases N1 and N2.
影响因子：
5.6
作者：
BOSSARTWHITAKER, P;CARSON, M;AIR, GM
通讯作者：
AIR, GM
N9亚型流感病毒神经氨酸酶和逃逸突变体的精细原子结构。
影响因子：
5.6
作者：
Tulip,WR;Varghese,JN;Baker,AT;vanDonkelaar,A;Laver,WG;Webster,RG;Colman,PM
通讯作者：
Colman,PM
影响因子：
7.3
作者：
MAMMEN, M;DAHMANN, G;WHITESIDES, GM
通讯作者：
WHITESIDES, GM