Synthesis of end-labeled multivalent ligands for exploring cell-surface-receptor-ligand interactions
Synthesis of end-labeled multivalent ligands for exploring cell-surface-receptor-ligand interactions
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DOI：
10.1016/s1074-5521(00)00060-0
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发表时间：
2000-01-01
影响因子：
--
通讯作者：
Kiessling, LL
中科院分区：
文献类型：
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作者：
Gordon, EJ;Gestwicki, JE;Kiessling, LL
背景：开环的分解聚合（ROMP）是生成独特材料的强大合成方法。 Ruthenium ROMP发起人的功能群耐受性允许合成各种生物活性聚合物。我们产生的多价配体抑制细胞表面L-选择素，该蛋白会介导淋巴细胞寄养和炎症中的白细胞募集。我们假设这些配体通过特定的多价结合与L-选择蛋白发挥作用。要检查这一点并开发一种用最终标签合成多价材料的通用方法，我们研究了功能化的烯醇醚作为悬崖引发的烤面包中的封盖剂：我们合成了一个双功能分子，该分子通过终止了ruthenium Intientientientientientient in of truthenium intinium othenenium intient of。反应。该试剂在一端含有一个烯醇醚，另一端含有屏蔽的羧酸。我们将荧光素衍生物结合到终端新糖聚合物中，该聚合物先前已被证明抑制了L-选择素功能。我们使用了荧光。显微镜以可视化新糖聚合物与显示L-选择素的细胞结合。我们的结果表明，新糖聚合物通过多价相互作用特异性与细胞表面L-选择蛋白特异性结合。结论：ruthenium启动的ROMP可用于生成由潜在功能组终止的生物活性，多价配体。官能化的聚合物可以用多种分子标签标记，包括荧光分子，生物素，脂质或抗体。使用此策略结合记者组合聚合物的能力在材料和生物科学中具有广泛的应用。
Background: Ring-opening metathesis polymerization (ROMP) is a powerful synthetic method for generating unique materials. The functional group tolerance of ruthenium ROMP initiators allows the synthesis of a wide range of biologically active polymers. We generated multivalent ligands that inhibit cell surface L-selectin, a protein that mediates lymphocyte homing and leukocyte recruitment in inflammation. We hypothesized that these ligands function through specific, multivalent binding to L-selectin. To examine this and to develop a general method for synthesizing multivalent materials with end-labels, we investigated functionalized enol ethers as capping agents in ruthenium-initiated ROMP.Results: We synthesized a bifunctional molecule that introduces a unique end group by terminating ruthenium-initiated ROMP reactions. This agent contains an enol ether at one end and a masked carboxylic acid at the other. We conjugated a fluorescein derivative to an end-capped neoglycopolymer that had previously been shown to inhibit L-selectin function. We used fluorescence. microscopy to visualize neoglycopolymer binding to cells displaying L-selectin. Our results suggest that the neoglycopolymers bind specifically to cell surface L-selectin through multivalent interactions.Conclusions: Ruthenium-initiated ROMP can be used to generate biologically active, multivalent ligands terminated with a latent functional group. The functionalized polymers can be labeled with a variety of molecular tags, including fluorescent molecules, biotin, lipids or antibodies. The ability to conjugate reporter groups to ROMP polymers using this strategy has broad applications in the material and biological sciences.