Issue 11, 2021

Synthesis and immunological evaluation of the unnatural β-linked mucin-1 Thomsen–Friedenreich conjugate

Abstract

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.

Graphical abstract: Synthesis and immunological evaluation of the unnatural β-linked mucin-1 Thomsen–Friedenreich conjugate

Supplementary files

Article information

Article type
Paper
Submitted
03 1 2021
Accepted
24 2 2021
First published
24 2 2021

Org. Biomol. Chem., 2021,19, 2448-2455

Synthesis and immunological evaluation of the unnatural β-linked mucin-1 Thomsen–Friedenreich conjugate

X. Wu, H. McFall-Boegeman, Z. Rashidijahanabad, K. Liu, C. Pett, J. Yu, M. Schorlemer, S. Ramadan, S. Behren, U. Westerlind and X. Huang, Org. Biomol. Chem., 2021, 19, 2448 DOI: 10.1039/D1OB00007A

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