Chemical modifications of myotoxic PLA2 from Porthidium hyoprora: evaluation of catalytic effect and the myotoxic, neurotoxic and inflammatory activities

• Grant number: 11/17971-3
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2011
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sergio Marangoni
• Grantee: Sergio Marangoni
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The snake venom has a mixture of functional molecules can be compared by analogy to a natural laboratory that develops and improves toxins through mutations and natural selection to maintain their species microevolution (defense and food). These toxins affect the prey's physiological system making it become paralyzed (neurotoxycity and myotoxicity) and do not run away from the place of attack and also starts the digestion of food easier prey of the serpent.In search of a new drug by comparison with modeling and chemical specificity for its target, the pharmaceutical industry can take 11 years to high cost. The snake venom toxins have high specificity for their target, are increasingly considered as biological models and has contributed to the knowledge of how each amino acid polypeptide chain participates in the expression of the biological molecule. So are increasingly used as pharmacological tools and as a prototype for the development of natural medicines, eg represented by captopril (potent hypotensive), designed from the peptide present in the venom of the snake Bothrops jararaca (GMP-bradkinin-potentiating factor). Peptide perfected over millions of years with the help of natural selection. The industrial strategy behind this is that it is a biological model of isolated and purified in the laboratory, having molecular homogeneity, characterized physico-chemically and subjected to pharmacological tests. All emerging result of this molecule can be attributed to their structural characteristics (obtained from the study of sequence homology) and contribute to the spatial organization of the molecule that is making a functional protein (Landers, P. 2004).This project intends to conduct the study of diversity in the expression of PLA2 present in venom Porthidium hyoprora, analyzing the possible differences with respect to their biological activities, such as neurotoxicity, myotoxicity and inflammatory effects. Correlating well, its structure and function through different techniques of protein chemistry and chemical modifications in specific waste. P. hyoprora is distributed mainly in tropical rain forests with high humidity, especially in lowland equatorial forests of the Amazon (Campbell and Lamar, 2004). (AU)