Quantitative structure-activity relationship study of food protein-derived calmodulin-binding peptides

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Previous works from my laboratory have confirmed the feasibility of producing protein hydrolysates that contain low-molecular weight (<1 kDa) calmodulin (CaM)-binding peptides through enzymatic hydrolysis of pea and flaxseed proteins. Due to their small size, the peptides have a high potential to be absorbed intact into the blood circulatory system; in vitro tests confirmed resistance to gastrointestinal digestive enzymes. The protein hydrolysates were shown to inhibit the activities of CaM-dependent metabolic enzymes such as protein kinase II (CaMKII) and nitric oxide synthases (NOS) that have been implicated in the pathogenesis of chronic diseases. The proposed research will use the protein hydrolysates as the raw materials to isolate and identify the structural characteristics of potent CaM-binding peptides. Peptides will be purified from the protein hydrolysates using ion-exchange chromatography and reverse-phase high pressure liquid chromatography methods. Amino acid sequence of peptides will be determined using liquid chromatography-mass spectrometry methods. In vitro tests will determine inhibitor (peptide) concentration that reduces enzyme (CaMKII, NOS, and phosphodiesterase) activity by 50% (IC50). The relationships between IC50 and amino acid sequence of peptides will be determined using partial least square regression modeling to provide new information on structure-function properties and locate potent peptide sequences within food proteins. Animal feeding experiments will determine the potential physiological benefits of the peptides. Results from these experiments will identify peptides that can be used to formulate therapeutic products against chronic diseases and provide technical support for the Canadian health and food industries. Information from structure-function studies will provide scientists with a platform for future design of more powerful therapeutic peptides or peptidomimetics. The proposed work will lead to the training of highly qualified personnel with interdisciplinary skills in Food Science and the Life Sciences.