| Grant number: | 03/09994-7 |
| Support type: | PRONEX Research - Thematic Grants |
| Duration: | July 01, 2004 - August 31, 2008 |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Cooperation agreement: | CNPq - Pronex |
| Principal Investigator: | Luiz Juliano Neto |
| Grantee: | Luiz Juliano Neto |
| Home Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| Co-Principal Investigators: | Adriana Karaoglanovic Carmona ; Maria Aparecida Juliano |
| Associated grant(s): | 07/50335-8 - Kohei Oda | Kyoto Institute of Technology - Japão, AV.EXT |
| Associated scholarship(s): | 07/57471-4 - Study of the metallo-peptidase PHEX involvement in physiological and pathophysiological processes, BP.PD |
Abstract
The project covers developments of organic syntheses focused on the peptides, peptideomimetics and amino acids and libraries of peptides aimed at the study of proteases. In view of the diversity of proteolytic enzymes that we will be dealing with and because of the involvement of the same in different physiological or physiopathological processes and the integration with organic chemistry and spectroscopic physics, we will be collaborating with 9 national and 15 international groups. Participating in this project in the first year there will be 4 post doctorate holders, 16 postgraduate students at doctorate level, 2 students at masters level and two students in scientific initiation. Based on our previous experiences, we will develop peptides of internally quenched fluorescence, with the donor-acceptor pair of ortho-aminobenzoic (Abz) - N-(2,4-dinitrophenyl)ethylenediamine (EDDnp). The following proteolytic enzymes will be studied: a) Serino proteases such as tissular and plasmatic kallikrein, catepsine G, human kallikrein 3 (PSA) and 6; b) Lysosomal catepsines F, K, H, S, V and X; c) Proteases of parasites of tropical diseases such as leishmaniasis and malaria, dengue virus, yellow fever and hepatitis C; d) Endooligopeptidases; e) metalloproteases, such as the converter enzyme of the angiotensine I and PHEX; f) convertases (Kex2, PC I, PC2, PC5/6 and furine). We will incorporate non natural aminoacids and we will alter the peptidic chain to obtain specific substrates and inhibitors for several of these proteolytic enzymes. This project also aims to study cell proteolysis using the substrates developed as well as the inhibitors. In addition, we will be running a laboratory for the culture of cells for these purposes, as well as cultivating cells that express the proteases we are interested in. As a result of the approaches we are taking with the peptides we will be undertaking physico-chemical measures with several of them to be obtained, with the aim of drawing some parallel between the form and the function of the same in the interaction with the proteases. Other programs are still in analysis and planning and which could broaden this project: a) Proteolysis in germinative processes in plant seeds and/or apoptosis. b) Sourcing and study of keratinolytic proteases for industrial use. (AU)