A Modular Chemoenzymatic Synthesis of Disialosyl Globopentaosylceramide (DSGb5Cer) Glycan
| Autor: | Yu-Ju Shen, Jih Ru Hwu, Yan-Ting Kuo, Avijit K. Adak, Chun-Cheng Lin, Pei-Jhen Li, Dung-Yeh Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Glycan Glycosylation Ganglioside Globosides biology 010405 organic chemistry Chemistry Organic Chemistry Oligosaccharides Total synthesis Oligosaccharide 010402 general chemistry 01 natural sciences 0104 chemical sciences carbohydrates (lipids) Biochemistry Polysaccharides biology.protein Moiety lipids (amino acids peptides and proteins) |
| Zdroj: | The Journal of Organic Chemistry. 85:15920-15935 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/acs.joc.0c01091 |
| Popis: | The total synthesis of the oligosaccharide moiety of disialosyl globopentaosylceramide (DSGb5 Cer), a dominant ganglioside isolated from malignant renal cell carcinoma tissues, is reported. The synthetic strategy relies on a chemical α(2,6)-sialylation at the internal GalNAc unit of a Gb5 pentasaccharide backbone that furnishes a Neu5Acα(2,6)GalNAc-linked hexasaccharide, suitable for an enzymatic α(2,3)-sialylation of the terminal Gal residue to construct a heptasaccharide glycan. Convergent access to this key α(2,6)-sialylated hexasaccharide was also achieved through a [3+3] glycosylation building upon a Galβ(1,3)[Neu5Acα(2,6)]GalNAc-based trisaccharide donor and a Gb3 acceptor. The synthetic DSGb5 glycan bearing a 6-azidohexyl aglycon at the reducing end could undergo further regioselective functionalization. This approach represents a viable chemoenzymatic method for accessing complex ganglioside glycans and should be useful for the synthesis and biological investigation of DSGb5 derivatives. |
| Databáze: | OpenAIRE |
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