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血管紧张素转换酶(angiotensin converting enzyme,ACE)通过作用于维持血压正常的肾素-血管紧张系统(rennin-angiotensin system,RAS)和激肽释放酶-激肽系统(kallikrein-kinin system,KKS),使其失衡导致血压升高.而ACE活性抑制肽可以竞争性地与ACE的活性中心结合,从而抑制ACE的活性,使血压降低.天然来源的ACE抑制肽与传统的降压药物相比效果较好,无毒副作用,对正常血压没有影响,对于高血压的治疗和人类健康具有重要意义.本文以酪蛋白中提取的ACE活性抑制肽KVLPVP为先导肽,根据ACE抑制肽的结构特点,设计合成一系列的类ACE肽(similar ACE-like peptides).利用反相高效液相色谱法(RP-HPLC)直接测定其体外ACE抑制活性.结果表明,当芳香性的氨基酸残基Phe、Tyr、His和疏水性Val残基位于C-端时会提高多肽的ACE抑制活性,尤其是His位于C-端时,ACE抑制活性更强.通过对比先导肽与所合成的类ACE肽的ACE活性抑制率,可以发现,类ACE肽的ACE活性抑制率均高于先导肽.基于不同氨基酸残基位于C-端时对多肽的ACE抑制活性的研究,可以为降血压药物分子设计和筛选提供基础.
Angiotensin converting enzyme (ACE) acts by acting on renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) , Make it unbalanced lead to high blood pressure.And ACE activity inhibitory peptide can compete with ACE active center, thus inhibiting the activity of ACE, so that blood pressure.Central origin of ACE inhibitory peptides compared with traditional antihypertensive drugs Good, non-toxic side effects, has no effect on the normal blood pressure, for the treatment of hypertension and human health is of great significance.In this paper, extracted from casein ACE inhibitory peptide KVLPVP as the leader peptide, according to ACE inhibitory peptide structural characteristics, design A series of similar ACE-like peptides were synthesized and their in vitro ACE inhibitory activities were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). The results showed that when the aromatic amino acid residues Phe, Tyr, His and hydrophobic Val residues at the C-terminal enhance the ACE inhibitory activity of the peptide, especially when His is at the C-terminal. By comparing the ACE activity of the leader peptide with the synthetic ACE-like peptide The inhibitory rate of ACE activity of ACE-like peptides was higher than that of the leader peptide.The study of ACE inhibitory activity of peptides based on different amino acid residues located at the C-terminal could provide a basis for the design and screening of antihypertensive drug molecules .