Searching for a potential drug against cancer: design of anti angiogenic compounds based on the structure of human methionine aminopeptidase type-2

• Grant number: 98/11905-2
• Support Opportunities: Scholarships abroad - Research
• Start date: March 01, 1999
• End date: February 28, 2001
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Maria Cristina Nonato
• Grantee: Maria Cristina Nonato
• Host Investigator: Jon Chardy
• Host Institution: Pessoa Física
• Institution abroad: Cornell University, United States

Abstract

The present project aims at the structure-based drug design of antiangiogenic compounds, as a promising therapy against cancer. The target macromolecule is the human methionine aminopeptidase 2, involved in the tumor cell proliferation, and the lead compound is fumagillin, a natural fungal metabolite. A complete MetAP-2 characterization will be performed through the crystal structural determination of the enzyme in complex with different inhibitors, metal cofactors and natural substrate. Computational methods will be used for predicting a tighter, more specific and presumably less toxic ligand for human Met AP-2, a potential drug against cancer. (AU)