| Autor: |
Wu X; National Glycoengineering Research Center, Shandong University, Qingdao, Shandong 266237, China., McFall-Boegeman H, Rashidijahanabad Z, Liu K, Pett C, Yu J, Schorlemer M, Ramadan S, Behren S, Westerlind U, Huang X |
| Jazyk: |
angličtina |
| Zdroj: |
Organic & biomolecular chemistry [Org Biomol Chem] 2021 Mar 21; Vol. 19 (11), pp. 2448-2455. Date of Electronic Publication: 2021 Mar 01. |
| DOI: |
10.1039/d1ob00007a |
| Abstrakt: |
MUC1 glycopeptides are attractive antigens for anti-cancer vaccine development. One potential drawback in using the native MUC1 glycopeptide for vaccine design is the instability of the O-glycosyl linkage between the glycan and the peptide backbone to glycosidase. To overcome this challenge, a MUC1 glycopeptide mimic has been synthesized with the galactose-galactosamine disaccharide linked with threonine (Thomsen-Friedenreich or Tf antigen) through an unnatural β-glycosyl bond. The resulting MUC1-β-Tf had a much-enhanced stability toward a glycosidase capable of cleaving the glycan from the corresponding MUC1 glycopeptide with the natural α-Tf linkage. The MUC1-β-Tf was subsequently conjugated with a powerful carrier bacteriophage Qβ. The conjugate induced high levels of IgG antibodies in clinically relevant human MUC1 transgenic mice, which cross-recognized not only the natural MUC1-α-Tf glycopeptide but also MUC1 expressing tumor cells, supporting the notion that a simple switch of the stereochemistry of the glycan/peptide linkage can be a strategy for anti-cancer vaccine epitope design for glycopeptides. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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