Studies on poisons and derivatives: identification of molecular targets for the development of anti-inflammatory compounds

• Grant number: 24/06373-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: GlaxoSmithKline
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Mario Andrés Rodríguez Pineda
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Company: Secretaria da Saúde (São Paulo - Estado). Instituto Butantan
• Associated research grant: 20/13139-0 - Centre of Excellence in New Target Discovery, AP.PCPE

Abstract

Chondrocyte aging is associated with the degeneration of articular cartilage and can beobserved in joint disease pathogenesis, such as rheumatoid arthritis and osteoarthritis.Pro-inflammatory cytokines play pivotal roles in the progression of those diseases. Westandardized a model of inflammation in chondrocytes for screening purposes. CENTDhas been focusing on the study of new inflammatory targets and the screening for anti-inflammatory compounds from our library of peptides derived from venoms. Severalsynthetic peptides derived from cytoprotective proteins were elected for their potentialanti-inflammatory effects in several cell models such as chondrocytes, synoviocytes,and macrophages. Our group recently identified potential targets, identified as cellularproteins able to link to the anti-inflammatory peptides (P4, E8, D3, C-Ambly). Tocharacterize the key signaling pathways responsible for immuno-modulatory function,we are working on the knockout (KO) and knockdown target-validation strategies toelucidate the anti-inflammatory potential of the new targets. Furthermore, obtaining therecombinant form of new targets is essential for structure-activity studies and the studyof the nature of the target/peptide bond.