Structure and function study of angiotensin converting enzyme 2 (ACE2) activating peptides from food proteins

我的计划整合了发现研究，高素质的人才的培训，以实现了解食品蛋白质衍生的生物活性肽的结构-活性关系的目标。生物活性肽是蛋白质的小片段，可能具有改善人类健康和预防慢性疾病的巨大潜力。这些肽在蛋白质中是无活性的，但可以在食品加工和/或消化过程中释放。我以前的研究进展通过发现赠款研究了生物活性肽的结构和活性与血管紧张素转换酶（ACE）抑制，抗氧化和抗炎特性的关系。ACE负责血管紧张素II（Ang II）的产生，而其同系物ACE 2参与树脂血管紧张素系统中Ang II降解为Ang（1-7）。升高的Ang II水平引起氧化应激、炎症和血管收缩，导致高血压;因此ACE 2被认为在平衡Ang II的有害作用中起重要作用。抑制ACE是一种公认的血压控制方法;许多食物蛋白质衍生的抗高血压肽的特征在于ACE抑制。ACE抑制肽IRW是最近发现的ACE 2激活肽，而另外两个肽IQW和LKP没有ACE 2激活活性。这促使我们进一步研究ACE 2激活肽的结构特征和ACE抑制活性。由于ACE抑制不是ACE 2活化肽的基本性质，因此需要从各种蛋白质来源鉴定ACE 2活化肽。ACE 2激活肽的结构特征将通过定量构效关系建模和对接研究进行研究。考虑到ACE 2对Ang II的平衡作用，将在小肌肉细胞和动物中测试代表性ACE 2活化肽的抗氧化和抗炎活性。该研究计划将对ACE 2激活肽的结构和功能特性进行基础性发现，这将进一步推进我们对食品蛋白质作为生物活性肽来源的潜力的理解。许多慢性病与饮食和生活方式有关。了解它们的作用机制将有助于将研究转化为开发生物活性肽作为功能性食品或对心血管疾病有益的营养品。心血管疾病是加拿大和全世界发病率和死亡率的主要原因。因此，探索以改善内皮功能为目标的新型抗氧化肽将有助于改善加拿大人的健康和健康。

My program integrates discovery research, with training of highly qualified personnel, to achieve the goal of understanding the structure-activity relationships of food protein-derived bioactive peptides. Bioactive peptides are small fragments of proteins that may have vast potential for improving human health and preventing chronic diseases. These peptides are inactive within the proteins but can be released during food processing and/or digestion. My previous research progresses through Discovery Grants have studied the structure and activity relationships of bioactive peptides with angiotensin converting enzyme (ACE) inhibitory, anti-oxidative, and anti-inflammatory properties. ACE is responsible for angiotensin II (Ang II) generation, while its homologue, ACE2, is involved in degradation of Ang II into Ang (1-7) in the resin angiotensin system. Elevated Ang II level causes oxidative stress, inflammation, and vasoconstriction, leading to high blood pressure; thus ACE2 is thought to play an important role in counterbalancing the harmful effects of Ang II. Inhibition of ACE is a well-established approach for blood pressure control; many food protein derived antihypertensive peptides are characterized based on ACE inhibition. ACE inhibitory peptide IRW was recently identified as an ACE2 activating peptide, however, other two peptides, IQW and LKP, did not show ACE2 activating activity. This prompted us further research question on the structural features of ACE2 activating peptides with concomitant ACE inhibitory activity. Since ACE inhibition is not an essential property of ACE2 activating peptides, there is a need to identify ACE2 activating peptides from various protein sources. Structural features of ACE2 activating peptides will be studied using quantitative structure and activity relationship modeling and docking study. Representative ACE2 activating peptides will be tested for their antioxidant and anti-inflammatory activities in small muscle cells and in animals, given the counterbalancing effect of ACE2 on Ang II. This research program will make fundamental discoveries on the structure and function properties of ACE2 activating peptides, which will further advance our understanding the potential of food proteins as sources of bioactive peptides. Many chronic diseases are diet and life-style related diseases. Understanding their mechanisms of action will facilitate the translation of research towards the development of bioactive peptides as functional foods or nutraceuticals with benefits for cardiovascular diseases. Cardiovascular disease is the leading cause of morbidity and mortality in Canada and worldwide. Therefore, exploration of novel antioxidant peptides targeting at improving endothelial function will help to improve the health and wellness of Canadian.