School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, SP, Brazil.
Chemistry Institute, São Paulo State University, Araraquara, SP, Brazil.
Peptides. 2018 Apr;102:1-7. doi: 10.1016/j.peptides.2018.01.015. Epub 2018 Feb 2.
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 μM, 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.
缓激肽增效肽（BPPs）是矛头蝮蛇毒液中一种重要的毒素。它们通过抑制血管紧张素转换酶（ACE）直接作用于肾素-血管紧张素-醛固酮系统。这种作用可能导致该物种中毒时出现低血压休克。因此，本研究的主要目标是固相合成一种存在于矛头蝮蛇毒液中的 BPP，并分别对其进行 ACE 抑制和降压活性的体外和体内特征分析。使用自动固相肽合成仪合成 LmrBPP9 肽，并通过反相快速蛋白液相色谱（FPLC）进行纯化。合成肽的体外 IC50 为 4.25±0.10μM，表现出很强的 ACE 抑制能力。体内研究表明，LmrBPP9 可引起血压降低，在正常血压和高血压大鼠中均有此作用，在后者中更为明显。这些结果与体外结果一致，表明合成肽 LmrBPP9 可能是开发新型抗高血压药物的潜在分子。
