Poster 128 - Tityus serrulatus hypotensive peptides (TsHpTP): Structural and functional features

Poster 128. Congresso da Sociedade Brasileira de Toxinologia, 8., Symposium of the Pan American Section of the International Society on Toxinology, 8., 2004, Angra dos Reis, Brasil. Abstracts... J. Venom. Anim. Toxins incl.Trop. Dis., 2004, 10, 3, p.487.

Tityus serrulatusHypotensive Peptides (TsHpTP): Structural And Functional Features.

^{1,2Pimenta, A.M.C.; ^1,2Verano-Braga, T.; ^1,2Almeida, F.M.; ^1,2Dutra, A.A.A.; ^2,3Bemquerer, M.P.; ⁴Paula, R.D.; ⁴Santos, R.A.S.; ⁵Bougis, P.E.; ⁵}Martin-Eauclaire, M.F. and ^1,2De Lima, M.E.

1 Núcleo de Biomoléculas, 2 Laboratório de Venenos e Toxinas Animais and 3 Laboratório de Enzimologia e Físico-Química de Proteínas, Depto. de Bioquímica e Imunologia, ICB, UFMG, Belo Horizonte, Brazil; 4 Laboratório de Hipertensão, Depto. de Fisiologia e Biofísica, ICB, UFMG, Belo Horizonte, Brazil and 5 CNRS UMR 6560, Institut Jean Roche, Faculté de Médecine (secteur nord), Marseille, France.

Facilities in using micro-scale analytical techniques, such as mass spectrometry and proteomics, has led to a novel approach to prospect bioactive molecules in animal venoms. This is based on a structural-guided prospection and can lead to discover of novel functional molecules that have not yet been visualized by conventional bioassays and pharmacological-guided methods. By this prospection approach, we were able to find peptides that form a new structural family in the venom of Brazilian scorpion Tityusserrulatus. Structurally, these are linear, random-coiled peptides, ranging approximately from 1190 to 2700 Da and have typical Bradykinin Potentiating Peptides (BPP) amino acid signatures at their carboxi-terminal extremity (Pro-Pro-Ala). Pharmacologically, these peptides act as hypotensive agents by potentiating Bradykinin as showed by a strong and long-lasting hypotensive activity when tested in rats. Five highly similar isoforms were identified and named Tityusserrulatus Hypotensins (TsHpT-I to TsHpT-V). Three synthetic analogs were constructed for deeper pharmacological characterization: TsHpT-I, TsHpT_17-25 and TsHpT_Ac17-25Am, which is acetylated at N-terminal and amidated at C-terminal. It was verified that the pharmacological activity of this peptide family is located towards its C-terminal end. Also, other synthetic analogs have been constructed to assign the minimal structure that keep the pharmacological features.