Synthesis of glycopolymers for microarray applications via ligation of reducing sugars to a poly(acryloyl hydrazide) scaffold.
Synthesis of glycopolymers for microarray applications via ligation of reducing sugars to a poly(acryloyl hydrazide) scaffold.
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DOI：
10.1021/ja103009d
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发表时间：
2010-07-28
影响因子：
15
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
--
作者：
Godula, Kamil;Bertozzi, Carolyn R.
在本文中，我们报告了一个通用的合成策略，利用对酰肼还原聚糖形成稳定的环状N-糖苷的固有反应性的糖共聚物的组装。我们开发了一种聚（丙烯酰肼）（PAH）支架，我们结合了各种还原聚糖，从简单的单糖和二糖到相当复杂的人乳和血液低聚糖。缀合在温和条件下以优异的连接效率和立体选择性方式进行，提供具有主要以其环状β-糖苷形式容纳的侧链聚糖的糖共聚物。利用通过RAFT聚合制备的生物素封端的PAH支架，我们迅速组装了一组glycopolymers，我们在链霉亲和素涂层的玻璃上微阵列。然后，我们证明了在这些微阵列中，糖聚合物配体结合凝集素根据其悬垂聚糖的结构。重要的是，使用我们的方法可以容易地制备含有生物学相关的支链寡糖（如唾液酸化Lewisx）以及硫酸化糖胺聚糖样表位的糖共聚物。
In this paper, we report on a general synthetic strategy for the assembly of glycopolymers that capitalizes on the intrinsic reactivity of reducing glycans toward hydrazides to form stable cyclic N-glycosides. We developed a poly(acryloyl hydrazide) (PAH) scaffold to which we conjugated a variety of reducing glycans ranging in structure from simple mono- and disaccharides to considerably more complex human milk and blood oligosaccharides. The conjugation proceeds under mild conditions with excellent ligation efficiencies and in a stereoselective manner, providing glycopolymers with pendant glycans accommodated mostly in their cyclic β-glycosidic form. Utilizing a biotin-terminated PAH scaffold prepared via RAFT polymerization, we quickly assembled a panel of glycopolymers that we microarrayed on streptavidin-coated glass. We then demonstrated that in these microarrays, the glycopolymer ligands bind lectins according to the structures of their pendant glycans. Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewisx, as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology.
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