title: Antibodies against mucin-based glycopeptides affect Trypanosoma cruzi cell invasion and tumor cell viability.
abstract: This study describes the synthesis of glycopeptides NHAc[βGal]-(Thr)2 -[αGalNAc]-(Thr)2 -[αGlcNAc]-(Thr)2 Gly-OVA (1-OVA) and NHAc[βGal-αGalNAc]-(Thr)3 -[αLacNAc]-(Thr)3 -Gly-OVA (2-OVA) as mimetics of both T. cruzi and tumor mucin glycoproteins. These glycopeptides were obtained by solid-phase synthesis, which involved the prior preparation of the protected glycosyl amino acids αGlcNAc-ThrOH (3), αGalNAc-ThrOH (4), βGal-ThrOH (5), αLacNAc-ThrOH (6), and βGal-αGalNAc-ThrOH (7) through glycosylation reactions. Immunizations of mice with glycopeptides 1-OVA and 2-OVA induced high antibody titers (1:16 000), as verified by ELISA tests, whereas flow cytometry assays showed the capacity of the obtained anti-glycopeptides 1-OVA and 2-OVA antibodies to recognize both T. cruzi and MCF-7 tumor cells. In addition, antisera induced by glycopeptides 1-OVA and 2-OVA were also able to inhibit T. cruzi fibroblast cell invasion (70 %) and to induce antibody-mediated cellular cytotoxicity (ADCC) against MCF-7 cells, with 50 % reduction of cell viability.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP (Brazil).
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Campo
authors.forename: Thalita B
authors.initials: TB
authors.lastname: Riul
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
authors.forename: Marcelo-Dias
authors.initials: MD
authors.lastname: Baruffi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology / Q000628:therapy*; D006020:Glycopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D009077:Mucins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D009369:Neoplasms / Q000737:chemistry / Q000276:immunology / Q000628:therapy*; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
chemical_list: D000906:Antibodies; D006020:Glycopeptides; D009077:Mucins; D010047:Ovalbumin
keywords: Trypanosoma cruzi; antibodies; antitumor agents; glycopeptides; mucins