LAUSR

As one of the four major classes of biomolecules (carbohydrate, protein, nucleotide, and lipid), carbohydrates are the most prominent features of the cell’s exterior. Carbohydrates and their conjugates (glycoproteins, glycolipids) play important roles in various biological processes, including inflammation and immune response, angiogenesis and tumor cell metastasis, viral and bacterial infection, and many other cell-cell communications [1, . Glycoscience has gained significant interest in biomedical research owing to their critical physiological functions. Through vast effort devoted by glycoscientists in recent decades, carbohydrate drugs pave the way to a non-ignorable area of the therapeutics world . Among the recorded carbohydrate drugs, natural polysaccharides represent the largest percentage of more than 75%, followed by oligosaccharides, monosaccharides and their derivatives, contributing an equal occupation of about 10%. Several types of carbohydrate-based antibiotics, such as aminoglycosides, macrolides, and glycosylated aromatic structures, have been used in the treatment of pathogenic bacterial infections. Clinical antitumor adjuvants benefited from their immunomodulatory effects and low cytotoxicity account for about 30% of the marketed carbohydrate drugs. Notably, approximately all of the adjuvants are first marketed in China as polysaccharides extracted from traditional Chinese medicinal plants or fungi . About 20% of the marketed carbohydrate drugs are exploited to treat blood and cardiovascular diseases. Heparin, a well-known highly sulfated glucosaminoglycan, has been widely used as injectable anticoagulant since 1940s. Additionally, the physiological properties of carbohydrates and glycomimetic drugs are also exploited for the treatment of gastro-intestinal diseases, virus infections and diabetes. The unique carbohydrate structures on the surface of invasive pathogens and the aberrant glycosylation on malignant cells make such carbohydrate moieties attractive immunotherapy targets. The carbohydrate-based vaccines against Streptococcus pneumonia, Neisseria meningitides, Haemophilus influenzae type b and Salmonella typhi Vi have been used successfully to prevent such bacterial infections. Inspired by the success of antibacterial glycoconjugate vaccines, carbohydrate-based conjugate vaccines for cancer, viruses, protozoans and fungi are currently under development . Notably, the applications of most polysaccharide derived drugs such as the antitumor adjuvants are regional restricted due to their mixed compositions, ambiguous mechanisms, and the difficulties in quality control. Thus, chemical glycobiology is emerging as a powerful sub-discipline of chemical biology, aiming at structure characterization, artificial synthesis, pharmacological mechanism investigation, and quality control of carbohydrate drugs. Tremendous efforts have been devoted to the structure characterization of polysaccharides derived from traditional Chinese medical plants and fungi possessing diverse bioactivities . GV-971, a mixture of oligosaccharides derived from brown algae, was structurally elucidated as oligomannate with the degree of polymerization from 2 to 10. In 2019, the oligomannate sodium GV-971 had received conditional marketing approval in China to improve cognitive function in mild to moderate Alzheimer’s disease . Furthermore, various efficient methods (sulfation, selenylation, phosphorylation, acetylation, and alkylation) have been developed for the modification of polysaccharides to generate novel bioactivities or enhance the original activities. The complexity of carbohydrates has hampered investigations of their pharmacological mechanisms which require homogeneous and well-defined carbohydrates. To deal with this challenge, glycochemists continuously explore carbohydrate chemistry and develop versatile methods to streamline the synthesis of complex carbohydrates, such as gold (I)-catalyzed glycosylation (Yu glycosylation) , preactivation-based one-pot glycosylation [8] and automated glycan assembly . Efficient synthesis of welldefined carbohydrates has significantly promoted the devel[Received on] 16-Aug.-2020 [Corresponding author] Tel: 86-510-85328229, E-mail: jianyin@ jiangnan.edu.cn The author has no conflict of interest to declare. Available online at www.sciencedirect.com