Minimização da estrutura primária do peptídeo TsHpt-I: Identificação dos resíduos de aminoácidos cruciais e da estrutura peptídica mínima para a manutenção de seus efeitos anti-hipertensivos

Abstract

Using a proteomic approach, a new structural family of peptides was put in evidence in the venom of the yellow scorpion Tityus serrulatus. T. serrulatus Hypotensins (TsHpt) are random-coiled linear peptides that act as bradykinin potentiating peptides (PPBs). Aiming to better understand the relationship between the primary structure of TsHpt-I (AEIDFSGIPEDIIKQIKETNAKPPA) and its capacity to potentiate the hypotensive effect of BK, some synthetic peptides were constructed using the C-terminal portion of TsHpt-I as model; TsHpt-I[17-25] (KETNAKPPA); TsHpt-I[21-25] (AKPPA); TsHpt-I[22-25] (KPPA); TsHpt-I[23-25] (PPA); TsHpt-I[22-24] (KPP); TsHpt-I[22-23] (KP); TsHpt-I[23-24] (PP); TsHpt-I[24-25] (PA) and TsHpt-I[ac22-24] (acKPP), which do not have the positive charge in the lysine radical. All synthetic peptides holding the doublet PP at the C-terminal could potentiate the hypotensive effect of BK, but only the analogs that have the lysine residue, could induce a transient hypotension when intravenously administrated in male rats, indicating that the positive charge located towards the radical of this amino acid residue is crucial for this cardiovascular effect. The capacity of these peptides to induce an endothelium and NO dependent vasorelaxating effect was either affected by the absence of this positive charge. Despite several PPBs inhibit ACE, TsHpt-I and the synthetic analogs could not inhibit this enzyme. This study has also demonstrated that the reduction of the primary structure of TsHpt-I does not significantly alter the biological effects of this native peptide, which could be interest by biotechnological purpose, as minimization of enzymatic hydrolysis points, as well as lowering production costs.