Sequence-Controlled Multi-Block Glycopolymers to Inhibit DC-SIGN-gp120 Binding
Sequence-Controlled Multi-Block Glycopolymers to Inhibit DC-SIGN-gp120 Binding
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DOI：
10.1002/anie.201300068
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Haddleton, David M.
中科院分区：
文献类型：
--
作者：
Zhang, Qiang;Collins, Jennifer;Haddleton, David M.
聚糖-蛋白质相互作用对于许多生理过程是必不可少的，包括细胞-细胞识别、细胞粘附、细胞信号传导、病原体鉴定和分化。树突状细胞特异性细胞间粘附分子-3-抓取非整合素（DC-SIGN; CD 209）是一种存在于巨噬细胞和树突状细胞亚群上的C型凝集素（碳水化合物结合蛋白），在许多细胞相互作用中起关键作用。DC-SIGN通过多价聚糖-蛋白质相互作用识别表面富含甘露糖的聚糖，从而与微生物和宿主分子结合，并作为多种病毒（如人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV））的靶标。[1]碳水化合物结合蛋白（CBP）已被认为是预防HIV感染的潜在候选杀微生物剂。[2]然而，天然CBP的分离由于其亲水性而相对困难，并且它们显示出对病毒的显著低亲和力。[3]因此，合成凝集素对于碳水化合物识别研究是有意义的。[5]或者，哺乳动物凝集素的非碳水化合物抑制剂可用于防止DC-SIGN和gp 120之间的相互作用。[6]多价配体的结构对碳水化合物与凝集素的结合有很大的影响，并且几个研究小组已经证明了线性聚合物对有效的凝集素结合的使用。[七]《中国日报》
Glycan-protein interactions are essential for many physiological processes including cell-cell recognition, cell adhesion, cell signalling, pathogen identification and differentiation. Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN; CD209) is a C-type lectin (carbohydratebinding protein) present on both macrophages and dendritic cell subpopulations and play a critical role in many cell interactions. DC-SIGN binds to microorganisms and host molecules by recognizing surface rich mannose containing glycans through multivalent glycan-protein interactions and serves a target for several viruses such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV).[1] Carbohydrate binding proteins (CBP) have been suggested as potential candidate microbiocides for the prevention of HIV infection.[2] However, the isolation of natural CBPs is relatively difficult due to their hydrophilic nature and they show notably low affinities to virus.[3],[4] and thus synthetic lectins are of interest for carbohydrate recognition studies.[5] Alternatively, non-carbohydrate inhibitors of mammalian lectins can be used to prevent the interaction between DC-SIGN and gp120.[6] The architectures of the multivalent ligands have a great effect on carbohydrate binding to lectins and the use of linear polymers on effective lectin binding has been demonstrated by several research groups.[7]