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In many human carcinomas, mucin-1 (MUC1) is overexpressed and aberrantly glycosylated, resulting in the exposure of previously hidden antigens. This generates new patient antibody profiles that can be used in cancer diagnosis. In the present study, we focused on the MUC1-associated Tn antigen (α-O-GalNAc-Ser/Thr) and substituted the GalNAc monosaccharide by a glycomimic to identify MUC1-based glycopeptides with increased antigenicity. Two different glycopeptide libraries presenting the natural Tn antigen or the sp2-iminosugar analogue were synthesized and evaluated with anti-MUC1 monoclonal antibodies in a microarray platform. The most promising candidates were tested with healthy and breast cancer sera aiming for potential autoantibody-based biomarkers. The suitability of sp2-iminosugar glycopeptides to detect anti-MUC1 antibodies was demonstrated, and serological experiments showed stage I breast cancer autoantibodies binding with a specific unnatural glycopeptide with almost no healthy serum interaction. These results will promote further studies on their capabilities as early cancer biomarkers.


Pablo A Guillen-Poza, Elena M Sánchez-Fernández, Gerard Artigas, José Manuel García Fernández, Hiroshi Hinou, Carmen Ortiz Mellet, Shin-Ichiro Nishimura, Fayna Garcia-Martin. Amplified Detection of Breast Cancer Autoantibodies Using MUC1-Based Tn Antigen Mimics. Journal of medicinal chemistry. 2020 Aug 13;63(15):8524-8533

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PMID: 32672464

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