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 янв 2021
Accepted
24 фев 2021
First published
24 фев 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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements