类ACE抑制肽的合成及其活性分析

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.

Antagonist Activities of Similar ACE-like Peptides In Vitro

Angiotensin converting enzyme (ACE) plays a physiological role in regulating of blood pressure. The failure of rennin-angiotensin system (RAS) and kallikrein kinin system (KKS) leads to increasing blood pressure. ACE inhibitory peptides hind to the active center of ACE, and are able to lowering of the blood pressure. Compared with the traditional antihypertensive drug, the ACE inhibitory peptides resemble natural products and have fewer side effects. Our ACE inhibitory peptide-like peptides were structurally designed and synthesized using KVLPVP as the precursor peptide, and detected in ACE activity assays by RP-HPLC.The activities were improved by the C-terminal amino acid residues such as the aromatic Phe, Tyr, His and hydrophobic Val. The aromatic residue His displlayed the most effective enhancing of ACE inhibition. These results showed that the ACE inhibition was more significant with the modified peptide, especially when converted from the precursor peptide.