Kondoh M, Furutani T, Azuma M, Ooshima H, Kato J
Department of Bioapplied Chemistry, Osaka City University, Japan.
Biosci Biotechnol Biochem. 1997 May;61(5):870-4. doi: 10.1271/bbb.61.870.
We searched our chemical collection to identify non-N-acetylneuraminate (NeuAC) inhibitors of influenza neuraminidase (NA). Of the 62 acyl derivatives tested, several acyl amino acids, but not acyl alkanolamine derivatives, were effective and inhibited the NA activity in a dose-dependent manner. N-3-Hydroxymyristoyl D-cysteine and N-myristoyl-O-caproyl-D-serine were the more potent compounds and inhibited the enzyme in a noncompetitive manner (Ki = 102 and 125 microM, respectively) without respect to the substrate. An important consideration for the choice of inhibitor is the selectivity of the inhibition. These compounds were selective inhibitors of viral NA and effective for any variant enzyme, but the enzymes from V. cholerae and human placenta were insensitive. Accordingly, the acyl amino acid derivatives may be expected to be inhibitors without cellular toxicity and may serve as lead compounds for anti-influenza agents.
我们在化学化合物库中进行筛选，以寻找流感病毒神经氨酸酶（NA）的非N-乙酰神经氨酸（NeuAC）抑制剂。在所测试的62种酰基衍生物中，几种酰基氨基酸具有抑制作用，呈剂量依赖性，而酰基链烷醇胺衍生物则无此作用。N-3-羟基肉豆蔻酰-D-半胱氨酸和N-肉豆蔻酰-O-己酰-D-丝氨酸是活性更强的化合物，它们对该酶的抑制作用不具有竞争性（Ki分别为102和125 microM），且与底物无关。选择抑制剂时的一个重要考虑因素是抑制的选择性。这些化合物是病毒NA的选择性抑制剂，对任何变异酶均有效，但对霍乱弧菌和人胎盘来源的酶不敏感。因此，酰基氨基酸衍生物有望成为无细胞毒性的抑制剂，并可作为抗流感药物的先导化合物。
