Chemoenzymatic Assembly of Mammalian O-Mannose Glycans
Chemoenzymatic Assembly of Mammalian O-Mannose Glycans
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哺乳动物 O-甘露糖聚糖的化学酶组装
DOI：
10.1002/ange.201804373
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hongzhi Cao
中科院分区：
文献类型：
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作者：
Caicai Meng;Aniruddha Sasmal;Yan Zhang;Tian Gao;Chang-Cheng Liu;Naazneen Khan;Ajit Varki;Fengshan Wang;Hongzhi Cao
O-甘露糖聚糖占脑中总O-聚糖的30%。以前的合成和功能研究仅集中在抗肌萎缩蛋白聚糖的核心M3 O-甘露糖聚糖上，其是各种肌肉疾病的致病因子。在这项研究中，开发了一种高效的化学酶促策略，首次集体合成了63个核心M1和核心M2 O-甘露糖聚糖。这种化学酶促策略的特征在于，以克级化学合成五种明智设计的核心结构，以及用三种酶模块对核心结构进行多样性取向的修饰，以提供不超过四个步骤的线性序列中的58种复合O-甘露糖聚糖。合成的O-甘露糖聚糖与一组凝集素、抗体和脑蛋白的结合谱也通过使用打印的O-甘露糖聚糖阵列进行了探索。
O-Mannose glycans account up to 30% of total Oglycans in the brain. Previous synthesis and functional studies.have only focused on the core M3 O-mannose glycans of adystroglycan, which are a causative factor for various muscular.diseases. In this study, a highly efficient chemoenzymatic.strategy was developed that enabled the first collective synthesis.of 63 core M1 and core M2 O-mannose glycans. This.chemoenzymatic strategy features the gram-scale chemical.synthesis of five judiciously designed core structures, and the.diversity-oriented modification of the core structures with three.enzyme modules to provide 58 complex O-mannose glycans in.a linear sequence that does not exceed four steps. The binding.profiles of synthetic O-mannose glycans with a panel of lectins,.antibodies, and brain proteins were also explored by using.a printed O-mannose glycan array.