National Glycoengineering Research Center, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China.
Glycobiology Research and Training Center, University of California, San Diego, CA, 92093, USA.
Angew Chem Int Ed Engl. 2018 Jul 16;57(29):9003-9007. doi: 10.1002/anie.201804373. Epub 2018 Jun 25.
O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of α-dystroglycan, 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.
O-甘露糖聚糖占大脑中总 O-聚糖的 30%左右。以前的合成和功能研究仅集中于α- dystroglycan 的核心 M3 O-甘露糖聚糖，这是各种肌肉疾病的致病因素。在这项研究中，开发了一种高效的化学酶策略，首次实现了 63 个核心 M1 和核心 M2 O-甘露糖聚糖的集体合成。这种化学酶策略的特点是通过精心设计的五个核心结构的克级化学合成，以及通过三个酶模块对核心结构进行多样化修饰，以线性序列提供不超过四个步骤的 58 种复杂 O-甘露糖聚糖。还通过打印的 O-甘露糖聚糖阵列探索了合成 O-甘露糖聚糖与一系列凝集素、抗体和脑蛋白的结合谱。
