Nawaz K A Ayub, David Swapna Merlin, Murugesh Easwaran, Thandeeswaran Murugesan, Kiran Kalarikkal Gopikrishnan, Mahendran Ramasamy, Palaniswamy Muthusamy, Angayarkanni Jayaraman
Department of Microbial Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India.
Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India.
Phytomedicine. 2017 Dec 1;36:1-7. doi: 10.1016/j.phymed.2017.09.013. Epub 2017 Sep 27.
Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases.
HYPOTHESIS/PURPOSE: Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives.
The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension.
Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking.
The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver-Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE.
The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases.
植物是生物活性肽的重要来源。其中，血管紧张素转换酶（ACE）抑制肽因其预防高血压的能力而备受关注。抑制ACE已被确立为治疗与ACE相关疾病的有效方法。
假设/目的：一些合成的ACE抑制药物会产生副作用，因此人们一直对天然化合物作为替代品感兴趣。
本研究旨在从木豆中鉴定和表征一种具有抑制ACE生物学特性的肽分子，并将其开发为治疗高血压的方法。
用从变质奶糖中分离出的蛋白水解真菌黑曲霉发酵木豆（Cajanus cajan (L.) Millsp.）种子。提取物通过FPLC系统的尺寸排阻色谱法进行纯化。对显示出ACE抑制作用的馏分进行LC-MS/MS序列鉴定。通过分子动力学模拟分析肽的稳定性，并通过分子对接鉴定与ACE的相互作用位点。
该研究报道了一种新型的ACE抑制八肽Val-Val-Ser-Leu-Ser-Ile-Pro-Arg，分子量为869.53 Da。Lineweaver-Burk图表明该肽对ACE的抑制作用为竞争性模式。此外，分子对接和模拟研究表明该肽与ACE之间存在强而稳定的相互作用。
结果清楚地表明了该肽对ACE的抑制特性，因此可将其作为治疗高血压和其他与ACE相关疾病的治疗策略进行探索。
