Studies on Specific Ligands and Enzymes from Trypanosoma cruzi

• Grant number: 95/04562-3
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 1996
• End date: February 28, 2001
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Walter Colli
• Grantee: Walter Colli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant(s): 97/06162-8 - Putative host cell receptors for Tc-85 glycoproteins from Trypanosoma cruzi, AR.EXT
• Associated scholarship(s): 97/08755-6 - Identification of the host cell receptor(s) for the Tc-85 glycoprotein family present on the surface of Trypanosoma cruzi using anti-idiotype antibodies, BP.DR

Abstract

In 1983 our laboratory described a glycoprotein of 85 kDa (Tc-85) which specific for the infective form of the parasite. The involvment of this glycoprotein with the T. cruzi invasiveness into host cells was confirmed by inhibition with specific monoclonal antibodies. This glycoprotein is polymorphic, with different isoelectric points among the different isoforms and is anchored via a lysoalkylfosfatidylinositol. As this protein exists in small amounts on the surface of T. cruzi we decided to characterize its receptor on the surface of the host cell using an antiidiotypic antibody raised against the monoclonal antibody H1A10 which inhibits the internalization of the parasite into host cells by 50-90%. This antibody is recognizing a protein on the surface of mammalian cells which is being presently characterized. Another approach was to study the interaction of Tc-85 with laminin. We have shown that the most acidic component of the Tc-85 family binds to this macromolecule of the extracellular matrix. We are presently sequencing the gene of Tc-85. The group is also interested in three enzymes of T. cruzi which are, apparently, specific for the parasite and does not exist in mammalian cells: galactofuranosidase and two enzymes of the trypanothione metabolism: trypanothione peroxidase and trypanothione transferase. Studies on the galactofuranosidase are being conducted in collaboration with Dr. Rosa Muchnik de Lederkremer, from the University of Buenos Aires. Studies with the enzymes of the trypanothione metabolism are being conducted in collaboration with the german group of Dr. Henryk Kalisz, investigador of the Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, with whom contacts have been made two years ago. These studies pretend to clone these enzymes, to study their kinetic properties, to crystallize the enzymes and try to design drugs able to interact with their active sites. (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)

CHUNG, MAN-CHIN; GUIDO, RAFAEL VICTÓRIO CARVALHO; MARTINELLI, TATIANE FAVARATO; GONÇALVES, MARINEI FERREIRA; POLLI, MICHELLE CARNEIRO; BOTELHO, KATIA CIRLENE ALVES; VARANDA, ELIANA APARECIDA; COLLI, WALTER; MIRANDA, M. TERÊSA M.; FERREIRA, ELIZABETH IGNE. Synthesis and in vitro evaluation of potential antichagasic hydroxymethyinitrofurazone (NFOH-121): A new nitrofurazone prodrug. Bioorganic & Medicinal Chemistry, v. 11, n. 22, p. 4779-4783, Nov. 2003. (95/04562-3, 01/01192-3)

ALMEIDA-DE-FARIA‚ M.; FREYMÜLLER‚ E.; COLLI‚ W.; ALVES‚ MJM. Trypanosoma cruzi: characterization of an intracellular epimastigote-like form. Experimental Parasitology, v. 92, n. 4, p. 263-274, 1999. (95/04562-3)