Development of effective inhibitors against carbohydrate recognition adhesion molecules involved in invasion of inflammatory cells and/or cancer cells.

1.我们首次成功地鉴定了多功能蛋白聚糖作为白细胞粘附分子L-选择素的配体。Versican是一种由成纤维细胞产生的大型硫酸软骨素蛋白聚糖。与L-选择素的其它配体不同，多功能蛋白聚糖不被唾液酸刘易斯X型碳水化合物修饰，但具有与L-选择素的凝集素结构域相互作用的硫酸软骨素侧链。Versican在生理条件下定位于肾脏远端小管的上皮细胞中，但在病理条件下从那里快速释放。脱落的多功能蛋白聚糖随后被白细胞L-选择素识别，这可能促进组织损伤。Versican不仅可以结合L-选择素，还可以结合其他炎性粘附分子，如P-选择素和CD 44。此外，它可以在其硫酸软骨素侧链上捕获某种类型的趋化因子，这可能导致增加炎症反应。结果表明，抑制L-选择素的功能可抑制输尿管梗阻引起的间质性肾炎.我们已经发现了一种物质，可以抑制岩藻糖基化和唾液酸化的细胞表面蛋白。

1. We have for the first time succeeded in identifying versican as a ligand for a leukocyte adhesion molecule, L-selectin. Versican is a large chondrotin sulfate proteoglycan produced by fibroblasts. Unlike other ligands for L-selectin, versican is not modified with sialyl Lewis X type carbohydrates, but has chondroitin sulfate side chains which interacts with the lectin domain of L-selectin. Versican is localized in epithelial cells of distal tubules of the kidney under physiological conditions, but is rapidly released from there under pathological conditions. The shed versican is then recognized by leukocyte L-selectin, which may promote tissue injury.2. Versican can bind to not only L-selectin but also other inflammatory adhesion molecules, such as P-selectin and CD44. In addition, it can capture a certain type of chemokines on its chondrotin sulfate side chains, which may result in augmenting inflammatory responses. It was revealed that functional inhibition of L-selectin leads to inhibition of interstitial nephritis induced by ureteral obstruction.3. We have found a substance that can inhibit fucosylation and sialylation of cell surface proteins.