Functional evaluation of CdtVEGF, the vascular endothelial growth factor from the Brazilian rattlesnake Crotalus durissus terrificus

• Grant number: 24/14618-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Isabela Gobbo Ferreira
• Supervisor: Andrew Benest
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Nottingham, University Park, England
• Associated to the scholarship: 23/11264-0 - Production by heterologous expression on Pichia pastoris and evaluation of the efficacy of a vascular endothelial growth factor and a serineprotease from snake venom, for the production of a new biopolimer with adhesive capacity, BP.PD

Abstract

Snake venoms are considered rich sources of compounds with important pharmacological actions. In this way, studying the diverse components allows to clarify the pathogeny of the envenoming and helps identifying molecules with great biotechnological applications. In Brazil, snakes from Crotalus genus, represented by the Crotalus durissus species, inhabit several regions of the country and their venoms are mostly composed by proteins (95%). Regarding the venom of Crotalus durissus terrificus, there are more abundant molecules (such as crotoxin) and other minor components, such as Vascular Endothelial Growth Factor (VEGF). This non-enzymatic homodimer named CdtVEGF presents a molecular mass of 25.5 kDa and it was isolated from the venom, corresponding to 2% of the total proteins. It has a fundamental role in angiogenesis, induction of vascular permeability and cellular migration. Covalent conjugation with Polyethylene glycols (PEG) molecules, leads to an increase of its molecular mass, increases water solubility, decreases the accessibility of immune cells, and protects it against proteases. Previous study with PEG-CdtVEGF demonstrated its capacity to induce cellular migration and decrease leukocyte recruitment. This research project aims to clarify the effects of native and PEGylated CdtVEGF on vascular system by analyzing receptor binding, phosphorylation and angiogenesis in animal model. The results obtained with this project will be able to further elucidate the molecular functions of CdtVEGF, which are of singular importance to reveal the potential of the molecule as a therapeutic agent for the treatment of ischemic pathologies, wound healing and/or as molecular tool for the study of vascular system pathologies.