LmrBPP9: A synthetic bradykinin-potentiating peptide from Lachesis muta rhombeata venom that inhibits the angiotensin-converting enzyme activity in vitro and reduces the blood pressure of hypertensive rats

Autor(es)

Pinheiro-Junior, Ernesto Lopes ^[1] ; Boldrini-Franca, Johara ^[1] ; Pires de Campos Araujo, Luciana Mattoso ^[1] ; Santos-Filho, Norival Alves ^[2] ; Bendhack, Lusiane Maria ^[1] ; Cilli, Eduardo Maffud ^[2] ; Arantes, Eliane Candiani ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Ribeirao Preto, SP - Brazil

^[2] Sao Paulo State Univ, Chem Inst, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 102, p. 1-7, APR 2018.
• Citações Web of Science: 3

Resumo

Bradykinin-potentiating peptides (BPPs) are an important group of toxins present in Lachesis muta rhombeata venom. They act directly at renin-angiotensin-aldosterone system, through the inhibition of angiotensin-converting enzyme (ACE). This action may contribute to the hypotensive shock observed during the envenoming by this species. Thus, the main goal of this study was the solid-phase synthesis of a BPP found in L. m. rhombeata venom and its in vitro and in vivo characterization in relation to ACE inhibition and hypotensive activity, respectively. The LmrBPP9 peptide was synthesized using an automated solid-phase peptide synthesizer and purified by reversed-phase fast protein liquid chromatography (FPLC). The in vitro IC50 of the synthetic peptide is 4.25 +/- 0.10 mu M, showing a great capacity of ACE inhibition. The in vivo studies showed that LmrBPP9 induces blood pressure reduction, both in normotensive and hypertensive rats, being more pronounced in the last ones. These results agree with the in vitro results, showing that the synthetic peptide LmrBPP9 is a potential molecule to the development of a new antihypertensive drug. (AU)

• Processo FAPESP: 14/16182-3 - Novas perspectivas funcionais de uma serinoprotease de Crotalus durissus collilineatus: ação sobre canais iônicos dependentes de voltagem
• Beneficiário: Johara Boldrini França
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/05538-1 - Síntese, caracterização, estudo do mecanismo de ação e análise de métodos de liberação do peptídeo pBthTX-I, nas formas monoméricas e diméricas
• Beneficiário: Norival Alves Santos Filho
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs