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Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7

文献类型：期刊论文

作者Liu, Yating1,2; Yan, Mengkun1,3; Wang, Minghui1; Luo, Shiwei1,2; Wang, Shasha1,2; Luo, Yawen1,3; Xu, Zhuojia1,3; Ma, Wenjing1,3; Wen, Liuqing1,2,3; Li, Tiehai1,2,3
刊名ACS CENTRAL SCIENCE
出版日期2024-01-24
卷号10期号:2页码:417-425
ISSN号2374-7943
DOI10.1021/acscentsci.3c01170
通讯作者Li, Tiehai(tiehaili@simm.ac.cn)
英文摘要Disialosyl globopentaosylceramide (DSGb5) is a tumor-associated complex glycosphingolipid. However, the accessibility of structurally well-defined DSGb5 for precise biological functional studies remains challenging. Herein, we describe the first total synthesis of DSGb5 glycolipid by an efficient chemoenzymatic approach. A Gb5 pentasaccharide-sphingosine was chemically synthesized by a convergent and stereocontrolled [2 + 3] method using an oxazoline disaccharide donor to exclusively form beta-anomeric linkage. After investigating the substrate specificity of different sialyltransferases, regio- and stereoselective installment of two sialic acids was achieved by two sequential enzyme-catalyzed reactions using alpha 2,3-sialyltransferase Cst-I and alpha 2,6-sialyltransferase ST6GalNAc5. A unique aspect of the approach is that methyl-beta-cyclodextrin-assisted enzymatic alpha 2,6-sialylation of glycolipid substrate enables installment of the challenging internal alpha 2,6-linked sialoside to synthesize DSGb5 glycosphingolipid. Surface plasmon resonance studies indicate that DSGb5 glycolipid exhibits better binding affinity for Siglec-7 than the oligosaccharide moiety of DSGb5. The binding results suggest that the ceramide moiety of DSGb5 facilitates its binding by presenting multivalent interactions of glycan epitope for the recognition of Siglec-7.
WOS关键词DIVERSITY-ORIENTED STRATEGY ; RENAL-CELL CARCINOMA ; ANTIGEN GLOBO-H ; CHEMICAL-SYNTHESIS ; GLYCOSPHINGOLIPIDS SYNTHESIS ; ENZYMATIC-SYNTHESIS ; GANGLIOSIDE DSGB5 ; ALPHA ; GALACTOSYLATION ; GLYCOSIDES
资助项目National Natural Science Foundation of China[22077130] ; National Natural Science Foundation of China[20ZR1467900] ; CAS Pioneer Talent Program, Shanghai Municipal Science and Technology Major Project, and Science and Technology Commission of Shanghai Municipality
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001162275300001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/309554]  
专题中国科学院上海药物研究所
通讯作者Li, Tiehai
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Yating,Yan, Mengkun,Wang, Minghui,et al. Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7[J]. ACS CENTRAL SCIENCE,2024,10(2):417-425.
APA Liu, Yating.,Yan, Mengkun.,Wang, Minghui.,Luo, Shiwei.,Wang, Shasha.,...&Li, Tiehai.(2024).Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7.ACS CENTRAL SCIENCE,10(2),417-425.
MLA Liu, Yating,et al."Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7".ACS CENTRAL SCIENCE 10.2(2024):417-425.

入库方式： OAI收割

来源：上海药物研究所

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