Divergent Synthesis of Core m1, Core m2 and Core m3 O-Mannosyl Glycopeptides via a Chemoenzymatic Approach
Divergent Synthesis of Core m1, Core m2 and Core m3 O-Mannosyl Glycopeptides via a Chemoenzymatic Approach
复制标题
通过化学酶法不同合成 Core m1、Core m2 和 Core m3 O → 甘露糖肽
DOI：
10.1002/cjoc.202200088
复制
发表时间：
2022-04-25
影响因子：
5.4
通讯作者：
Peng，Peng
中科院分区：
文献类型：
--
作者：
Li，Tianlu;Zhang，Youqin;Peng，Peng
O ‐甘露糖基化在调节各种生物过程中起着至关重要的作用，例如，大脑和肌肉发育。然而，由于其先天异质性，其确切功能在很大程度上仍然未知。在这方面，仍然欢迎开发有效的方法来获得不同结构定义的糖肽。在这项研究中，通过化学酶促策略实现了O-甘露糖基α-肌营养不良聚糖（α-DG）糖肽的多样性导向组装。该策略的特点是：（i）通过审慎设计的保护基策略和化学糖苷化，以克级差异合成核心m1、核心m2和核心m3甘露糖基化氨基酸;（ii）通过优化的微波辅助固相肽合成（SPPS）进行有效的糖肽组装;以及（iii）酶促加工核心聚糖结构，以安装半乳糖基和唾液酸-半乳糖基部分。这种化学酶促方法的效率和灵活性，证明了与不同的核心m1，核心m2和核心m3甘露糖聚糖，包括核心m2糖肽轴承七糖的第一次12糖肽的建设。
Comprehensive SummaryO‐Mannosylation plays a vital role in the regulation of a variety range of biological processes, for instance, brain and muscle development. However, the precise function remains largely unknown due to its innate heterogeneity. In this regard, it is still welcome to develop efficient methods to access diverse structurally‐defined glycopeptides. In this study, a diversity‐oriented assembly ofO‐mannosyl α‐dystroglycan (α‐DG) glycopeptides has been achieved via a chemoenzymatic strategy. This strategy features (i) gram scale divergent synthesis of core m1, core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation; (ii) efficient glycopeptide assembly via the optimized microwave‐assisted solid phase peptide synthesis (SPPS); and (iii) enzymatic elaboration of the core glycan structures to install galactosyl and sialyl‐galactosyl moieties. The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1, core m2 and core m3 mannosyl glycans, including a core m2 glycopeptide bearing a heptasaccharide for the first time.