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

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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.