A PROTEOMIC APPROACH TO PROSPECT NEW STRUCTURAL FAMILIES OF BIOACTIVE PEPTIDES IN Tityus serrulatus SCORPION VENOM

Pimenta, A.M.C.(1,4), Mansuelle, P.(1), Stocklin; R.(2), Favreau, P.(2), Diniz, C.R.(3), De Lima, M.E.(4), Bougis, P.E.(1), Martin-Eauclaire, M.F.(1)

(1)Laboratoire de Biochimie - Ingénierie des Protéines, UMR 6560, Marseille, France, (2)Atheris Laboratoires, Geneve, Switzerland, (3)Centro de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Brazil, (4)Laboratório de Venenos e Toxinas Animais, Departamento de Bioquímica e Imunologia, ICB, UFMG, Belo Horizonte, Brasil

Scorpion venoms are a rich mixture of peptides that act in many fronts from ionic channels in excitable tissues to cardiovascular and respiratory systems. Due their lethality, long toxins that alters the closing and opening kinetics of Na⁺ channels, called respectively alpha and beta-toxins, were firstly described and are well known. Those toxins are peptides ranging from 6000 to 7000 Da, constrained by four disulfide bonds and more representative in a quantitative sense. Smaller peptides, ranging from 3500 to 4500 Da, folded by three or four disulfide bonds, are known as K⁺-channels toxins and have a higher variability in terms of primary structure. To date, less than 15 sequences were completely established for both Na⁺- and K⁺- channel toxins in Tityus serrulatus venom. Besides, different peptide families that could respond to a variety of biological activities other than well known neurotoxic effects, have been neglected. Here, we describe novel biologically active peptides belonging to different structural families, discovered by a structurally driven approach. By using different liquid chromatography/mass spectrometry coupled platforms in a proteomic approach, we were able to screen for new molecules in T. serrulatus venom. At least 380 molecular masses were observed only in toxic fractions of this venom. On plate enzymatic digestions followed by MALDI-TOF mass spectrometry analysis, were also used to establish structural features of some peptides.

Support: CAPES/COFECUB, CNRS, INSERM, CNPq and FAPEMIG. 

CORRESPONDENCE TO:

Maria Elena de Lima Perez Garcia, Avenida Cel. José Dias Bicalho, 516 apto. 101, Belo Horizonte, MG, CEP: 31.275.050, Brasil, Email: delima@icb.ufmg.br