Research topic: Chemical glycobiology drives the discovery of carbohydrate-based drugs

Dr. YIN Jian is now a Professor of Glycoscience at Jiangnan University. His research interests cover chemical synthesis of complex oligo/polysaccharides, development of carbohydrate-based vaccines, drugs, and drug delivery systems. In the past five years, he has published 34 peer-reviewed articles as a corresponding author including J Am Chem Soc, Angew Chem Int Ed, Adv Funct Mater, Chem Sci, Chem Commun, etc. He has applied for 23 Chinese patents of invention with eight already authorized. In addition, nine PCT patents were claimed, and two U.S. patents have been issued. He won the 3rd China “Zhang Shuzheng Glycoscience Award” in 2019.

Title:Chemical glycobiology drives the discovery of carbohydrate-based drugs
[Abstract] In this issue, we are pleased to publish four original articles covered a specific range of chemical glycobiology topics including the investigation of carbohydrate reaction characteristics, synthesis of carbohydrate analogues, and discovery of pharmaceutical active polysaccharides. The issue begins with a paper reported the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines via the Lattrell-Dax epimerization. Zhang ZP et al. describe the synthesis and bioactivity of novel carbohydrate-triazole derivatives. Ding HM et al. provide a study on effect of Sargassum fusiforme polysaccharide on apoptosis and its possible mechanism in human erythroleukemia cells. Kim JY et al. study on the phytoglycoprotein isolated from Dioscorea batatas Decne.Despite the structural complexity of carbohydrates, chemical glycobiology based on rapidly developed carbohydrate chemistry has driven the discovery of a vast array of carbohydrate-based drugs for the treatment of a variety range of human diseases. However, more efforts should be put on the study of precise mechanisms and active domains, as well as automated synthesis of complex carbohydrates. Additionally, modification and simulation of natural carbohydrates, targeted drug delivery based on recognitions of carbohydrates by receptors, and synthetic carbohydrate-based vaccines are all highly potential approaches for the future development of carbohydrate-based drugs. It’s anticipated that chemical glycobiology will be one of the most successful fields of novel drug development and play a key role in the treatment of human diseases.

Title:Anomeric configuration-dependence of the Lattrell-Dax epimerization from D-glucose to synthetically useful D-allose derivatives
[Abstract] D-Allose and its derivatives play important roles in the field of health care and food nutrition. Pure and well-defined D-allose derivatives can facilitate the elucidation of their structure-activity relationship as an essential step for drug design. The Lattrell-Dax epimerization, refers to the triflate inversion using nitrite reagent, is known as valuable method for the synthesis of rare D-allose derivatives. Here, the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines via the Lattrell-Dax epimerization was studied. For C3 epimerization of D-glucose derivatives bearing O2-acyl group, an anomeric configuration-dependent acyl migration from O2 to O3 was found. In addition, a neighbouring group participation effect-mediated SN1 nucleophilic substitution of the D-glucosamine bearing C2 trichloroacetamido (TCA) group in the Lattrell-Dax epimerization was dependent upon anomeric configuration. Thus, the effect of anomeric configuration on the Lattrell-Dax epimerization of D-glucose suggests that β-D-glucosides with low steric hindrance at C2 should be better substrates for the synthesis of D-allose derivatives. Significantly, the efficient synthesis of the orthogonally protected D-allose 13 and D-allosamine 18 will serve well for further assembly of complex glycans.

Title:Novel carbohydrate-triazole derivatives as potential α-glucosidase inhibitors
[Abstract] A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC50 74.0 ± 1.3 μmol·L−1) than acarbose. The molecular docking revealed that compound 10f could bind to α-glucosidase via the hydrophobic, π-π stacking, and hydrogen bonding interactions. The results may benefit further structural modifications to find new and potent α-glucosidase inhibitors.

Title:Phytoglycoprotein isolated from Dioscorea batatas Decne promotes intestinal epithelial wound healing
[Abstract] Dioscorea batatas Decne (DBD) has been used to heal various illnesses of the kidney and intestine as an herbal medicine in Asia. As a source of therapeutic agents, many glycoproteins have been isolated from mushrooms and plants, but the functional role of glycoprotein in intestinal epithelial wound healing has not been understood yet. In the present study, we investigated the wound healing potentials of the 30 kDa glycoprotein (DBD glycoprotein) isolated from DBD in human intestinal epithelial (INT-407) cells. We found that DBD glycoprotein (100 μg·mL−1) significantly increased the motility of INT-407 cells for 24 h by activating protein kinase C (PKC). DBD glycoprotein stimulated the activation of p38 mitogen-activated protein kinase (MAPK), which is responsible for the phosphorylation of NF-κB inhibitor α (IκBα). DBD glycoprotein increased the level of profilin-1 (PFN1), α-actinin and F-actin expression via activation of transcription factor, nuclear factor-kappa B (NF-κB) during its promotion of cell migration. Experimental mouse colitis was induced by adding dextran sulfate sodium (DSS) to the drinking water at a concentration of 4% (W/V) for 7 days. We figured out that administration of DBD glycoprotein (10 and 20 mg·kg−1) lowers the levels of disease activity index and histological inflammation in DSS-treated ICR mice. In this regard, we suggest that DBD glycoprotein has ability to promote the F-actin-related migration signaling events via activation of PKC and NF-κB in intestinal epithelial cells and prevent inflammatory bowel disease.

Title:Effect of Sargassum fusiforme polysaccharide on apoptosis and its possible mechanism in human erythroleukemia cells
[Abstract] This study aimed to investigate the effects of Sargassum fusiforme polysaccharide (SFPS I, II, and III) on the apoptosis and regulation of human erythroleukemia (HEL) cells. The effect of different doses of SFPS on HEL cell growth was detected using the Cell Counting Kit-8 method, and apoptosis was detected by Hoechst staining. Cell cycle distribution and apoptosis were detected using flow cytometry. Expression of the cell cycle gene, p53, antiapoptotic genes, Bcl-xL and Bcl-2, and pro-apoptotic genes, Bax, Bad, and Caspase-3, as well as the expression of the corresponding proteins, were detected using real-time quantitative polymerase chain reaction (qPCR) and Western blot. The results showed that SFPS II and III decreased HEL cell viability and induced HEL cell apoptosis. Different concentrations of SFPS (I, II, and III) were detected that induced much less toxic effect in normal human embryonic lung (MRC-5) cells, and SFPS I increased cell proliferation, indicating its favorable selectivity towards cancer cells. The mechanism by which SFPS induced apoptosis was also found to be related to the induction of cell cycle arrest in the G0/G1 phase and the increased expression of apoptosis-related genes and proteins. We concluded that SFPS induces HEL cell apoptosis, possibly via activation of the Caspase pathway, providing the theoretical basis for the development of SFPS-based anti-tumor drug products.