Antibodies against Mucin-Based Glycopeptides Affect Trypanosoma cruzi Cell Invasion and Tumor Cell Viability

作者：Campo Vanessa L; Riul Thalita B; Carvalho Ivone^*; Baruffi Marcelo Dias

来源：ChemBioChem, 2014, 15(10): 1495-1507.

DOI：10.1002/cbic.201400069

• antibodies
• antitumor agents
• glycopeptides
• mucins
• Trypanosoma cruzi

This study describes the synthesis of glycopeptides NHAc-[beta Gal]-(Thr)(2)-[alpha GalNAc]-(Thr)(2)-[alpha GlcNAc]-(Thr)(2)Gly-OVA (1-OVA) and NHAc[beta Gal-alpha GalNAc]-(Thr)(3)-[alpha LacNAc]-(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 alpha GlcNAc-ThrOH (3), alpha GalNAc-ThrOH (4), beta Gal-ThrOH (5), alpha LacNAc-ThrOH (6), and beta Gal-alpha GalNAc-ThrOH (7) through glycosylation reactions. Immunizations of mice with glycopeptides 1-OVA and 2-OVA induced high antibody titers (1: 16000), 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.

• 出版日期2014-7-7