Scholarship 16/04699-7 - Neoplasias, Células tumorais - BV FAPESP
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Synthesis of mucin glycopeptide containing tumor antigen analogue with potential therapeutic applications in cancer

Grant number: 16/04699-7
Support Opportunities:Scholarships in Brazil - Master
Start date: September 01, 2016
End date: February 28, 2018
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Ivone Carvalho
Grantee:Marcelo Fiori Marchiori
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/19390-0 - Development of mucin glycoconjugates with diagnostic and therapeutic applications in muscular dystrophies and cancer, AP.JP

Abstract

Mucins are glycoproteins WITH high molecular weight that possess as fundamental characteristic linkage between sugar ±GalNAc and amino acid residues Ser/Thr (±GalNAc-Ser/ Thr). In tumors mucin production is dysregulated, once their biosynthetic mechanisms are impaired with consequent alteration in the O-glycosylation pattern. As result abnormal and incomplete glycans are formed, which are continuously expressed in tumor cells and generally absent in healthy tissues. The incessant exposure of these glycans give them the name of Tumor Antigens Carbohydrates Associated ("TACAS"), such as Tn (±GalNAc-Ser/Thr), sialyl-Tn (STn - Neu5Ac-Tn) and TF (²Gal1-3±GalNAc-Ser/Thr) antigens. Among tumor mucins, MUC1 is the most extensively investigated and is composed of tandem repeat regions HGVTSAPDRPAPGSTAPPA sequence with five potential sites for O-glycosylation (O-±GalNAc). In view of the importance of the "TACAS" as tumor markers of clinical significance, these are used in clinical trials as therapeutic vaccines, but with limited success due to their low immunogenicity. Thus, considering their constant presence in tumor mucins such as MUC1, synthetic glycopeptides that not only mimic the peptide sequence of the MUC1 type (PDTRPAP), but also possess TACAS analogs linked to their peptide chain have high potential for application in the development of anti-tumor vaccines. Thus, the aim of this project is the synthesis and immunogenic activity evaluation of glycoconjugate Neu5Ac±2-triazole-6-±GalNAc-Thr-Arg-Pro-Ala-Pro-GlyOH 19, mimicking mucin MUC1 type tumors, which will be obtained by glycosylation reactions and solid phase synthesis.

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Scientific publications
(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, . (12/19390-0, 16/04699-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MARCHIORI, Marcelo Fiori. Synthesis of mucin glycopeptide, containing tumor antigen analog, with possible therapeutic applications in cancer. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.