Development of peptidomimetic compounds for the treatment of retinopathy

• Grant number: 16/22645-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2017 - May 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Ricardo Jose Giordano
• Grantee: Ricardo Jose Giordano
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Roberto Kopke Salinas

Abstract

Angiogenesis, the formation of new blood vessels from pre-existing ones, is an important process in vertebrate organisms, in physiological and pathological conditions. Retinopathy, a primary reason for legal blindness in adults, is an example in which angiogenesis has a key role in disease formation and progression. Macular degeneration and diabetic and retinopathy of prematurity are disease that affect all ages, races and social classes, an has an important impact in Brazilian and worldwide health care systems, since it affect young working adults. Drugs that prevent the formation of angiogenic blood vessels in the retina have been effective in the treatment of these disease. In previous work, financed by a young investigator award from FAPESP, we have established in our laboratory animal models to study that recapitulate different aspects of human retinopathy. Using these models and combinatorial approaches (phage display), we have identified a small hexapeptide with anti-angiogenic properties and inhibitor of tyrosine kinase receptors belonging to the VEGF family (Michaloski et al., Science Advances, in press). In this novel project, we aim to extend these studies to map the binding site for this peptide within the VEGF receptors. By combining phage display and nuclear magnetic resonance methods, we will design peptidomimetic compounds based on our newly discovered peptide, and in the process, develop novel peptidomimetic inhibitor of pathological angiogenesis. (AU)