Characterization and structural optimization of protein target ligands related to inflammatory processes studied by CRID

• Grant number: 23/01133-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2023
• End date: December 31, 2023
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Ariane Fernandes Bertonha Delezuk
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Inflammatory diseases represent a complex and heterogeneous group of disorders that cause morbidity and mortality worldwide. In this context, the Center for Research in Inflammatory Diseases (CRID/USP) has a unique role. The discovery of multiple molecular targets for these diseases is an example of their work. Some of these targets are the proteins: hPKM2, hKMO, hIDO-1 and hPAD4. In HTS campaigns, over 7,000 chemical samples were tested for each target. HITs were found for all studied targets. The HITs were submitted to activity confirmation assays through concentration-response curves (IC50) and crystallographic studies with the KMO and PKM2 complexes. Therefore, the center aims to discover and plan the synthesis of new molecules capable of satisfactorily modulating the activity of these target proteins. The present work plan has the goal to select, isolate and characterize the best HITs specialized metabolites, in addition to SAR, LBDD and SBDD evaluations, and planning the synthesis of analogues to improve the properties of HITs.