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Search for new substrates and / or inhibitors for EP24.15 and EP24.16 in the low molecular weight fractions of the Tityus serrulatus scorpion venom.

Grant number: 11/15472-0
Support Opportunities:Scholarships in Brazil - Master
Start date: March 01, 2012
End date: March 31, 2013
Field of knowledge:Health Sciences - Collective Health - Public Health
Principal Investigator:Vanessa Rioli
Grantee:Bruno Duzzi
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Accidents caused by scorpion pose a serious public health problem in Brazil. In fact, the number of accidents involving human subjects has increased in recent years. In Brazil, most of the fatalities resulting from accidents are caused by Tityus serrulatus scorpions. This is due to the frequency of their occurrence and their potential to induce severe clinical manifestations. Despite the potency of its venom, what is currently known about its molecular components is restricted to neurotoxins acting on ion channels, and there is little information about other biologically active peptides. In this study we intend to analyze the venom of Tityus serrulatus as a source of peptides that can interact with metalopeptidases of pathophysiological importance, such as oligopeptidases neurolysin (EP 24.16) and thimet-oligopeptidase (EP 24.15). These enzymes have been specially selected becausem of the symptons observed on the clinical picture after the bite. The venom of T. serrulatus is capable of prodution a variety of effects on excitable tissues because of its role in the peripheral nervous system where it increases the release of neurotransmitters. The activity of oligopeptidases on nervous system cells and other molecules (ie neurotensin and angiotensin) may explain the peaks of tension (either hyper or hypo) in poisoned patients, as described by Chipaux and Goyfroon (2008). The methodology to be employed for the isolation of these new substrates and / or inhibitors will be the one previously described (Rioli et al., 2003) and patented (Rioli V., Ferro E.S., registration PI0301511 PTO-4, 16/05/2003) by the proponent. The use of this strategy for the isolation of new substrates / inhibitors is also based on the recent finding that the biggest number of drugs recently approved or pending approval by the FDA is made up of peptides of natural origin.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DUZZI, Bruno. Search for new substrates and/or inhibitors of thimet oligopeptidase (EC3.4.24.15) and neurolysin (EC3.4.24.16) enzymes in low molecular weight fractions of Tityus serrulatus scorpion venom.. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.