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Analysis of the mechanism of action involved in the selective activity of Abe III 1.3 in voltage-dependent K+ channels

Grant number: 11/21031-6
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): January 01, 2012
Effective date (End): June 30, 2012
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Jose Eduardo Pereira Wilken Bicudo
Grantee:Diego Jose Orts y Belato
Supervisor abroad: Jan Tytgat
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Leuven (KU Leuven), Belgium  
Associated to the scholarship:09/07128-7 - Sea anemones neurotoxins as tools to study the physiology of voltage-gated potassium channels, BP.MS

Abstract

Sea anemones venom are a rich source of bioactive compounds, including peptide toxins which are tools for studying the structure and function of voltage-gated K+ channels (KV). During the first year of my MSc project (FAPESP 2009/07128-7), we performed a peptidomic analysis of the venom of the sea anemone Actinia bermudensis and characterized the activity of the peptide Abe III 1.3 through a wide screening in 11 KV channel subtypes (KV 1.1-1.6, KV 2.1, KV 4.2, KV 4.3, Shaker IR and hERG). Abe III 1.3 is selective to KV 1.1 and 1.2, with IC50 values of 705.23 +/- 12.3 nM and 53.78 +/- 3.45 nM, respectively. Abe III 1.3 is composed of 17 amino acids that are connected by two disulfide bonds. Our results suggest that Abe III 1.3 is a novel type of sea anemone toxin that acts on KV. These results together with further biochemical and electrophysiological experiments proposed in this research project will help to understand the relationship between the structure of Abe III 1.3 and its selective-activity. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ORTS, DIEGO J. B.; PEIGNEUR, STEVE; SILVA-GONCALVES, LAIZ COSTA; ARCISIO-MIRANDA, MANOEL; BICUDO, JOSE EDUARDO P. W.; TYTGAT, JAN. AbeTx1 Is a Novel Sea Anemone Toxin with a Dual Mechanism of Action on Shaker-Type K+ Channels Activation. MARINE DRUGS, v. 16, n. 10 OCT 2018. Web of Science Citations: 2.
ORTS, DIEGO J. B.; MORAN, YEHU; COLOGNA, CAMILA T.; PEIGNEUR, STEVE; MADIO, BRUNO; PRAHER, DANIELA; QUINTON, LOIC; DE PAUW, EDWIN; BICUDO, JOSE E. P. W.; TYTGAT, JAN; DE FREITAS, JOSE C. BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker. FEBS Journal, v. 280, n. 19, p. 4839-4852, OCT 2013. Web of Science Citations: 15.
ORTS, DIEGO J. B.; PEIGNEUR, STEVE; MADIO, BRUNO; CASSOLI, JULIANA S.; MONTANDON, GABRIELA G.; PIMENTA, ADRIANO M. C.; BICUDO, JOSE E. P. W.; FREITAS, JOSE C.; ZAHARENKO, ANDRE J.; TYTGAT, JAN. Biochemical and Electrophysiological Characterization of Two Sea Anemone Type 1 Potassium Toxins from a Geographically Distant Population of Bunodosoma caissarum. MARINE DRUGS, v. 11, n. 3, p. 655-679, MAR 2013. Web of Science Citations: 17.

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