A Synthetic MUC1 Glycopeptide Bearing GalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells

Author(s)

Campo, Vanessa Leiria ; Riul, Thalita B. ; Bortot, Leandro Oliveira ; Martins-Teixeira, Maristela B. ; Marchiori, Marcelo Fiori ; Iaccarino, Emanuela ; Ruvo, Menotti ; Dias-Baruffi, Marcelo ; Carvalho, Ivone

• Document type: Journal article
• Source: CHEMBIOCHEM; v. 18, n. 6, p. 527-538, MAR 16 2017.
• Web of Science Citations: 4

Abstract

This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing GalNAc-SerOBn and GalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (GalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr{[}GalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr{[}GalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing GalNAc-Thr or GalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with GalNAc-glycopeptide 4-BSA induced higher sera titers (1:320000) than immunizations with GalNAc-glycopeptide 3-BSA (1:40000). Likewise, flow cytometry assays showed higher capacity of the obtained anti-glycopeptide 4-BSA antibodies to recognize MCF-7 tumor cells. Cross-recognition between immunopurified anti-GalNAc antibodies and GalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that GalNAc-glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4-BSA, bearing GalNAc-Thr as Tn antigen isomer. (AU)

• FAPESP's process: 12/19390-0 - Development of mucin glycoconjugates with diagnostic and therapeutic applications in muscular dystrophies and cancer
• Grantee: Vanessa Leiria Campo
• Support Opportunities: Research Grants - Young Investigators Grants