Structural characterization of the human phosphatases PTP-1B and PP2A, involved in cancer, and their interactions with inhibitors

• Grant number: 11/03054-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2011
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ricardo Aparicio
• Grantee: Valeria Scorsato
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Cancer is a leading cause of death today, and the second cause of accidental death in Brazil, where government funds for treatment of the desease exceed 1 billion reals per year. In many cases, treatments and anticancer therapies are not totally effective, thus being extremely important to develop new therapies or improve the existing ones. The development of modulators of the activity of proteins overexpressed in tumors is a major area of research in this direction. In particular, the protein phosphatases PP2A and PTP-1B have been identified as important targets for developing anticancer therapies. These proteins are involved in cell signaling pathways and are overexpressed in many types of malignant tumors. This project aims to evaluate, through a structural, biochemical and thermodynamic approach, the ability to inhibit and to characterize the interaction of PTP-1B and PP2A with families of new chemical compounds synthesized at the Institute of Chemistry/UNICAMP. The results to be achieved will contribute to a better understanding of the interaction and selectivity of the compounds, giving support for chemical modifications of the lead compounds to obtain more potent and selective inhibitors. (AU)

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)

SCORSATO, VALERIA; LIMA, TATIANI B.; RIGHETTO, GERMANNA L.; ZANCHIN, NILSON I. T.; BRANDAO-NETO, JOSE; SANDY, JAMES; PEREIRA, HUMBERTO D'MUNIZ; FERRARI, ALLAN J. R.; GOZZO, FABIO C.; SMETANA, JULIANA H. C.; et al. Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus. SCIENTIFIC REPORTS, v. 6, AUG 4 2016. (11/03054-9)

FONSECA, EMANUELLA M. B.; TRIVELLA, DANIELA B. B.; SCORSATO, VALERIA; DIAS, MARIANA P.; BAZZO, NATALIA L.; MANDAPATI, KISHORE R.; DE OLIVEIRA, FABIO L.; FERREIRA-HALDER, CARMEN V.; PILLI, RONALDO A.; MIRANDA, PAULO C. M. L.; et al. Crystal structures of the apo form and a complex of human LMW-PTP with a phosphonic acid provide new evidence of a secondary site potentially related to the anchorage of natural substrates. Bioorganic & Medicinal Chemistry, v. 23, n. 15, p. 4462-4471, AUG 1 2015. (10/17544-5, 11/03054-9, 09/51602-5, 11/15792-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SCORSATO, Valeria. Regulation of protein phosphatases involved in cancer: structural studies of TIPRL and its interaction with protein phosphatase 2A. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.