Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters.

Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters.
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DOI:
10.1021/ja9078539
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发表时间:
2009-12-16
影响因子:
15
通讯作者:
Wang, Lai-Xi
Wang, Lai-Xi
中科院分区:
化学1区
文献类型:
--
作者:
Huang, Wei;Wang, Denong;Yamada, Masao;Wang, Lai-Xi

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N-聚糖是许多糖蛋白的主要成分。这些糖部分经常通过与各种聚糖结合蛋白(GBP)的相互作用参与重要的生理和疾病过程。聚集效应是许多聚糖-凝集素相互作用的重要特征。本文描述了一种新型N-聚糖簇的化学酶促合成方法,该方法使用串联内切糖苷酶催化的转糖基化。发现N-聚糖核心中的内部β-1,2-连接的GlcNAc部分一旦暴露在非还原末端,就能够作为Endo-A和EndoM-N175 A催化的转糖基化的受体。这种有效的化学酶促方法允许糖链的快速延伸以形成一类聚糖簇,其中糖残基全部通过天然N-聚糖中发现的天然糖苷键连接。此外,在两个GlcNAc残基的区别性酶促反应可以实现,以提供新的杂交簇。凝集素微阵列研究揭示了糖表位表达的不寻常的属性,由这个小组的结构明确的合成N-聚糖。这些新化合物可能对功能糖组学研究有价值,以揭示聚糖和碳水化合物结合蛋白的新功能。
N-glycans are major components of many glycoproteins. These sugar moieties are frequently involved in important physiological and disease processes via their interactions with a variety of glycan-binding proteins (GBP). Clustering effect is an important feature in many glycan-lectin interactions. We describe in this paper a chemoenzymatic synthesis of novel N-glycan clusters using a tandem endoglycosidase-catalyzed transglycosylation. It was found that the internal β-1,2-linked GlcNAc moieties in the N-glycan core, once exposed in the non-reducing terminus, was able to serve as acceptors for transglycosylation catalyzed by Endo-A and EndoM-N175A. This efficient chemoenzymatic method allows a quick extension of the sugar chains to form a class of glycan clusters in which sugar residues are all connected by native glycosidic linkages found in natural N-glycans. In addition, a discriminative enzymatic reaction at the two GlcNAc residues could be fulfilled to afford novel hybrid clusters. Lectin microarray studies revealed unusual properties in glyco-epitope expression by this panel of structurally well-defined synthetic N-glycans. These new compounds are likely valuable for functional glycomics studies to unveil new functions of both glycans and carbohydrate-binding proteins.
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