Exploring structure-function relationship of DHODH enzyme in the development of ne...
| Grant number: | 05/51966-6 |
| Support type: | BIOTA-FAPESP Program - Regular Research Grants |
| Duration: | February 01, 2006 - January 31, 2009 |
| Field of knowledge: | Biological Sciences - Biophysics |
| Principal Investigator: | Otavio Henrique Thiemann |
| Grantee: | Otavio Henrique Thiemann |
| Home Institution: | Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil |
Abstract
In order to discover new pharmacologically active compounds for target diseases, I two strategies can be adopted in parallel: One is the screening in biological or biochemical assays of large numbers of extracts or pure compounds, both from natural sources and compound libraries, while the other strategy involves the computational search of libraries of compounds with the aid of the 30 crystal structure of the target enzyme or using the chemical structure of known bioactive compounds. The probability of finding positive hits of bioactive compounds depends on the number and diversity of the samples screened and the diversity of assays employed. After a compound is identified, the structural characterization may be required. A substantial part of the effort in lead compound identification and improvement is dedicated to the analysis of the interactions of the compound with its target enzyme. These studies require the building of compound data bases and of advanced tools in medicinal chemistry. The present proposal aims to implement biochemical assays known as High Throughput Screening (HTS), using automated systems and small sample volumes, contributing with the overall effort of the BioprospecTa network. The organization of compound data bases were the chemical and structural information as well as the inhibitory activity of each compound will be organized allowing the application of advanced medicinal and computational methods for the identification and further optimization of hits and lead compounds. At present, we are performing biological screenings in collaboration with the natural product chemistry laboratories of Prof. Or. Paulo Cezar Vieira (DQ-UFSCar), Prof. Dr. Roberto Gomes de Souza Berlinck (DFQ-IQSC) and Prof. Dr. Monica Tallarico Puppo (FMRP). The major goal of the research developed in the Laboratory is to perform both applied and basic research as well as technological development. This effort focuses in areas of Structure-Based Molecular Design, specifically and directly related to the BioprospecTa initiative, in the rational design of new structure-based compounds and in protein engineering. (AU)