Fast Access to Robust C-Sialoside Multimers
Fast Access to Robust C-Sialoside Multimers
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DOI：
10.1002/chem.200801810
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Beau, Jean-Marie
中科院分区：
文献类型：
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作者：
Papin, Caroline;Doisneau, Gilles;Beau, Jean-Marie
细胞表面糖缀合物和受体之间的相互作用在广泛的生物学事件中起着至关重要的作用，其中聚糖在细胞表面作为许多不同排列的集合呈现。这部分解释了为什么大多数基于聚糖的相互作用需要多价性来实现生物学上显著的相互作用。[1]N-乙酰神经氨酸（Neu 5Ac）是唾液酸家族的主要成员[2-4]，通常作为α-酮糖苷键连接的末端糖位于细胞表面糖缀合物上。由于这种在糖缀合物中的外部位置，它参与了许多生物现象，[3，4]包括人类细胞与细菌和病毒的病理相互作用。[5]这导致了对唾液酸化学的强烈研究兴趣，[6]包括设计针对流感病毒的有效化疗药物[7]或制定可以促进快速准确检测病毒的诊断工具。[8]诊断构建体对外部条件和靶标的酶活性的稳定性通常是严重的和被低估的问题。[9]In在这种情况下，我们已经开发了一系列新的寡价C-唾液酸糖苷连接到不同的支架上，能够提供不同的化合价和几何形状的组合，可以有效地与各种生物靶标相互作用。通过使用非常短的合成途径结合两个高产关键步骤制备了定义明确的低聚C-唾液酸苷结构：我们最近报道的钐介导的Reformatsky偶联反应，使用异头乙酸酯1 [10]（方案1）和铜（I）催化的叠氮化物和炔的Huisgen环加成反应，[11]“点击”化学的模型反应。[12]这种高度区域选择性的反应引入了1，4-二取代的1，2，3-三唑单元[13]连接，有效地降低了反应温度。
Interactions between cell-surface glycoconjugates and receptors play a crucial role in a wide range of biological events with a presentation of glycans at cell surfaces as an ensemble of many different arrangements. This explains in part why most glycan-based interactions necessitate multivalency to achieve a biologically significant interaction.[1] N-Acetylneuraminic acid (Neu5Ac), the major member of the sialic acid family,[2–4] is commonly located as an α-ketosidically linked terminal sugar on cell surface glycoconjugates. As a result of this external position within glycoconjugates, it is involved in numerous biological phenomena,[3, 4] including pathological interactions of human cells with bacteria and viruses.[5] This has led to intense research interest in sialic acid chemistry,[6] comprising the design of potent chemotherapeutic agents against the influenza virus [7] or the elaboration of diagnostic tools that could facilitate fast and accurate virus detection.[8] The stability of the diagnostic constructs to external conditions and to enzymatic activities of the target is often a serious and under-evaluated problem.[9]In this context, we have developed a collection of new oligovalent C-sialosides attached to different scaffolds able to provide diverse combinations of valency and geometry that could effectively interact with various biological targets. The well-defined oligomeric C-sialoside structures were prepared by using a very short synthetic pathway combining two highyielding key steps: our recently reported samarium-mediated Reformatsky-coupling reaction by using anomeric acetates 1 [10](Scheme 1) and the copper (I)-catalyzed Huisgen cycloaddition of azide and alkyne,[11] a model reaction of the “click” chemistry.[12] This highly regioselective reaction introduces 1, 4-disubstituted 1, 2, 3-triazole units [13] linking, effi-