Synthesis and evaluation of fluorescent Trypanosoma cruzi GPI anchors in support of drug discovery for Chagas' disease

• Grant number: 16/14192-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 06, 2017
• End date: January 05, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ivone Carvalho
• Grantee: Ana Luísa Malaco Morotti
• Supervisor: Rob Field
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: John Innes Centre, England
• Associated to the scholarship: 14/21200-0 - Synthesis and evaluation of the potential inhibitory activity of carbohydrates that mimic GPI anchor of T. cruzi, BP.DR

Abstract

Chagas disease affects millions of people worldwide, being a strong cause of morbidity and mortality, particularly in developing countries. Low financial returns and reduced income of affected individuals do not arouse interest in research and development of new treatments by the pharmaceutical industry. The therapeutic arsenal for Chagas disease is scarce and often ineffective, calling attention to the search for new compounds and more selective parasite molecular targets. Glycophosphatidylinositol (GPI) anchors are responsible for anchoring important T. cruzi proteins and glycoproteins, such as mucins and trans-sialidase, in the parasite's cell surface. Several studies have shown that these molecules are important for invasion and survival of parasite in host. In this context, synthesis of fluorescent T. cruzi GPI anchor moieties becomes an interesting tool for further studies to establish the biological functions and interactions performed by this class of molecules. The understanding of these molecular mechanisms will give clues to the design of parasite GPI anchor biosynthesis which will impact on host cell invasion and parasite survival.