title: A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells.
abstract: This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing βGalNAc-SerOBn and βGalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr[αGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr[βGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing αGalNAc-Thr or βGalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with βGalNAc-glycopeptide 4-BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc-glycopeptide 3-BSA (1:40 000). 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-βGalNAc antibodies and αGalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that βGalNAc-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 βGalNAc-Thr as Tn antigen isomer.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leiria Campo
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Thalita B
authors.initials: TB
authors.lastname: Riul
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Oliveira Bortot
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maristela B
authors.initials: MB
authors.lastname: Martins-Teixeira
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fiori Marchiori
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134, Napoli, Italy.|Second University of Naples, via Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Iaccarino
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134, Napoli, Italy.
authors.forename: Menotti
authors.initials: M
authors.lastname: Ruvo
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Dias-Baruffi
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café S/N, CEP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000917:Antibody Formation / Q000187:drug effects*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001681:Biological Assay / Q000592:standards; D002240:Carbohydrate Sequence; D006801:Humans; D007536:Isomerism; D061986:MCF-7 Cells; D051379:Mice; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D060327:Solid-Phase Synthesis Techniques; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D018396:Mucin-1; C040286:Tn antigen
keywords: MUC1-mucins; Tn antigen; antibodies; cancer vaccines; glycopeptides