Synthesis of a series of novel homo-and hetero-glycoclusters and their binding activities to DC-SIGN

一系列新型同形及杂合糖簇的合成及DC-SIGN结合活性研究

As a dendritic cell-specific C-type lectin receptor, DC-SIGN plays an important role in the early stages of many viral infections, including HIV and Ebola, making it an interesting therapeutic target. It has been found that DC-SIGN can recognize both highly mannosylated and branched fucosylated oligosaccharides. Herein, we synthesized a new series of homo-and Man-Fuc heteroglycoclusters with diverse structures. The binding properties of these compounds to tetrameric extracellular DC-SIGN were assessed by surface plasmon resonance(SPR). Heteroglycocluster 17 b showed high DC-SIGN-binding activity(K;= 2.6 μM). The structural determinants of this high affinity of 17 b were rationalized by docking and compared with its much less potent isomer 17 a. Therefore, 17 b might serve as a base for the development of potent inhibitors of DC-SIGN-dependent viral infection.

DC-SIGN是星形细胞特异性C-型凝集素受体,在诸如HIV,Ebola等多种病毒早期感染阶段起着重要作用,因而可能成为有价值的治疗靶标。研究发现,DC-SIGN可以识别高甘露糖结构以及含有岩藻糖分支的寡糖。据此,合成了一系列新型的具有结构多样性的同形及甘露糖-岩藻糖杂合糖簇,并采用表面等离子共振技术(SPR)对此类化合物进行了DC-SIGN胞外结构域四聚体的结合活性测试。结果表明,杂合糖簇17b显示了较高的DC-SIGN结合活性(KD=2.6μM)。采用分子对接的方法,以低活性的异构体17a为对照,对17b的活性进行了结构因素方面的评价与解释。17b可能作为基础用于研发DC-SIGN依赖的病毒感染抑制剂。