Synthesis of asymmetrical multiantennary human milk oligosaccharides
Synthesis of asymmetrical multiantennary human milk oligosaccharides
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DOI：
10.1073/pnas.1701785114
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发表时间：
2017-07-03
影响因子：
11.1
通讯作者：
Boons, Geert-Jan
中科院分区：
文献类型：
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作者：
Prudden, Anthony R.;Liu, Lin;Boons, Geert-Jan
尽管哺乳动物聚糖通常具有高度复杂的不对称多触角结构，但化学和化学-酶促合成几乎完全集中于制备更简单的对称结构。这种缺陷阻碍了对聚糖结合蛋白的生物学的研究，这反过来又使这类生物分子的生物医学用途复杂化。在此，我们描述了一种酶促策略，使用有限数量的人糖基转移酶，以获得60个不对称的，多触角的人乳低聚糖（HMO），这是用来开发聚糖微阵列的集合。用几种聚糖结合蛋白探测阵列发现，不仅末端糖表位，而且聚糖的复杂结构可以以意想不到的方式影响结合选择性。N-和O-连接的聚糖表达HMO的结构元件，因此，报道的合成原理将具有广泛的适用性。
Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemo-enzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability.