Developmental Research for New Medicines Based on Carbohydrate-cell Recognition

我们在分子水平上研究了流感病毒和白细胞粘附分子（选择素家族）对唾液寡糖的识别特异性。结果表明，1）唾液酸paragloboside是流感病毒识别的最佳底物之一，2）唾液酸-Lewis X和唾液酸-Lewis A都可以被所有选择素很好地识别。在此基础上，我们合成了一系列含1-脱氧野尻霉素的寡糖，并将其作为病毒感染和选择素结合的抑制剂。通过使用动物模型，已经发现一些N-烷基-1-脱氧野尻霉素-含唾液酸-和磺基-刘易斯X和-刘易斯A表位类似物是有效的抗炎剂。这些化合物的广泛治疗应用正在进行中。

We have examined the recognition specificity of sialooligosaccharides by influenza virus and leukocyte cell adhesion molecules (selectin family) at the molecular level. As a results, it has been shown that 1) sialyl paragloboside is one of the best substrate for influenza virus recognition, and 2) both sialyl-Lewis X and sialyl-Lewis A can be well recognized by all selectins. It was also found that sulfo-Lewis X and sulfo-Lewis A function as the selectin ligands with the equal or more afinity than the corresponding sialyl derivatives.Based on these results, a variety of novel oligosaccharides containing 1-deoxynojirimycin have been synthesized as the inhibitors of virus infection and selectin binding. Some of the N-alkyl-1-deoxynojirimycin-containing sialyl-and sulfo-Lewis X and -Lewis A epitope analogs have been found to be potent anti-inflammatory agents by using the animal models. A wide therapeutic application of these compounds is now in progress.