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Comprehensive Summary: O‐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 of O‐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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Heparan sulfate ( HS) is a highly sulfated glycosaminoglycan and exists in all animal tissues. HS and heparin are very similar, except that heparin has higher level of sulfation and higher content of iduronic acid. Despite the fact that it is a century-old drug, heparin remains as a top choice for treating thrombotic disorders. Pharmaceutical heparin is derived from porcine intestine or bovine lung via a long supply chain. This supply chain is vulnerable to the contamination of animal pathogens. Therefore, new methods for manufacturing heparin or heparin-like substances devoid of animal tissues have been explored by many researchers, among which, modifications of heparosan, the capsular polysaccharide of Escherichia coli K5 strain, is one of the promising approaches. Heparosan has a structure similar to unmodified backbone of natural HS and heparin. It is feasible to obtain HS or heparin derivatives by modifying heparosan with chemical or enzymatic methods. These derivatives display different biological activities, such as anticoagulant, anti-inflammatory, anticancer, and antiviral activities. This review focuses on the recent studies of synthesis, activity, and structure-activity relationship of HS/heparin-like derivatives prepared from heparosan. [ABSTRACT FROM AUTHOR]