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Development of mucin glycoconjugates with diagnostic and therapeutic applications in muscular dystrophies and cancer

Abstract

Hypoglycosylated ±-dystroglycan (±-DG) mucins are directly involved in pathological processes such as dystroglycanopathies (Congenital Muscular Distrophies - CMD) and epithelial tumors, while Tumor Associated Carbohydrate Antigens (TACAs)-containing glycopeptides, present in mucins of malignantly transformed cells, are super expressed in various tumor types, being considered potential targets for the development of synthetic antitumor vaccines. Currently, there is no available therapy for treatment of CMDs and the diagnostics for these dystroglycanopathies is based, mainly, on clinical manifestations associated with limited immunohistochemical methods. Regarding treatment and diagnostics of tumors, in Brazil, researches directed to the development of synthetic antitumor vaccines and monoclonal antibodies are still incipient and lagged if compared to other developed countries.Therefore, this project has as fundamental objective the insertion of a new transdisciplinary research line in Glycobiology at the Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP) directed to the chemical synthesis of glycoconjugates mimetics of ±-DG and tumor (TACAs) mucins as tools for development of new diagnostic and therapeutic strategies against muscular dystrophies and cancer. The consolidation of this proposal must be achieved by using different in solution and solid phase synthesis methods of glycopeptides, associated to biological assays involving the assembly of anti-±-DG and anti-TACAs antibodies by Phage Display, and their linkage to radioisotopes; and immunization assays of murine models and flow cytometry for evaluation of TACAs glycopeptide as potential antitumor vaccine. (AU)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARCHIORI, MARCELO F.; BORTOT, LEANDRO O.; CARVALHO, IVONE; CAMPO, VANESSA L. Synthesis of MUC1-derived glycopeptide bearing a novel triazole STn analog. Carbohydrate Research, v. 498, DEC 2020. Web of Science Citations: 0.
CANASSA-DELEO, THAIS; CAMPO, VANESSA LEIRIA; RODRIGUES, LILIAN CATALDI; MARCHIORI, MARCELO FIORI; FUZO, CARLOS; BRIGIDO, MARCELO MACEDO; SANDOMENICO, ANNAMARIA; RUVO, MENOTTI; MARANHAO, ANDREA QUEIROZ; DIAS-BARUFFI, MARCELO. Multifaceted antibodies development against synthetic alpha-dystroglycan mucin glycopeptide as promising tools for dystroglycanopathies diagnostic. GLYCOCONJUGATE JOURNAL, v. 37, n. 1, p. 77-93, FEB 2020. Web of Science Citations: 0.
MARCHIORI, MARCELO FIORI; IOSSI, GIULIA POMPOLO; BORTOT, LEANDRO OLIVEIRA; DIAS-BARUFFI, MARCELO; CAMPO, VANESSA LEIRIA. Synthesis of novel triazole-derived glycopeptides as analogs of alpha-dystroglycan mucins. Carbohydrate Research, v. 472, p. 23-32, JAN 15 2019. Web of Science Citations: 1.
CAMPO, VANESSA LEIRIA; MARCHIORI, MARCELO FIORI; CARVALHO, IVONE. Insights into Anti-Trypanasornal Agents Based on Synthetic Glycoconjugates. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 18, n. 5, p. 382-396, 2018. Web of Science Citations: 3.
MARCHIORI, MARCELO FIORI; RIUL, THALITA B.; BORTOT, LEANDRO OLIVEIRA; ANDRADE, PETERSON; JUNQUEIRA, GETULIO G.; FOCA, GIUSEPPINA; DOTI, NUNZIANNA; RUVO, MENOTTI; DIAS-BARUFFI, MARCELO; CARVALHO, IVONE; CAMPO, VANESSA LEIRIA. Binding of triazole-linked galactosyl arylsulfonamides to galectin-3 affects Trypanosoma cruzi cell invasion. Bioorganic & Medicinal Chemistry, v. 25, n. 21, p. 6049-6059, NOV 1 2017. Web of Science Citations: 3.
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. A Synthetic MUC1 Glycopeptide Bearing GalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells. CHEMBIOCHEM, v. 18, n. 6, p. 527-538, MAR 16 2017. Web of Science Citations: 4.
CAMPO, VANESSA L.; IVANOVA, IRINA M.; CARVALHO, IVONE; LOPES, CARLA D.; CARNEIRO, ZUMIRA A.; SAALBACH, GERHARD; SCHENKMAN, SERGIO; DA SILVA, JOAO SANTANA; NEPOGODIEV, SERGEY A.; FIELD, ROBERT A. Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion. Tetrahedron, v. 71, n. 39, SI, p. 7344-7353, SEP 30 2015. Web of Science Citations: 14.

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