Advances In Preparation Technology,structural Characteristics And Molecular Docking Of Grain-derived ACE Inhibitory Peptides

The food-derived Angiotensin-converting enzyme(ACE)inhibitory peptide is a functional resource of food which is potential to treat hypertensive diseases.The highly active structures of most ACE inhibitory peptide have not yet been determined,and the structural properties and SAR(structural-activity relationship)need to be further studied.Diseases such as hypertension have been increasing globally,becoming a life-threatening and urgent problem.Therefore,prevention and treatment of these diseases is an arduous task.ACE plays an important role in regulating blood pressure.It causes elevation of blood pressure by stimulating the formation of ACE and reliving degradation of hormones.Accordingly,inhibitors have become significant medication for clinical treatment of hypertension.In this thesis,the sequences of ACE inhibitory peptide derived from grains including rice,soybeans,wheat,corns,etc.were collected,and optimal methods and conditions for preparation of ACE inhibitory peptide were analyzed.It was found that soybean,rice bran and corns were fine resources of ACE inhibitory peptide.By summarizing the preparation methods,it was discovered that enzymatic hydrolysis was one of the decent methods of preparing grain-derived ACE inhibitory peptide by virtue of its outstanding advantages.Further analysis showed that the enzymolysis effect of alkaline protease was relatively better.It was able to further boost the efficiency of preparation if the enzymatic hydrolysis was assisted by ultrasound.Through analysis of the structural characteristics of amino acid sequences,including molecular weight,peptide chain length and terminal amino acid,it is concluded that most grain-derived ACE inhibitory peptides are 2-7 peptides,and the molecular weights are at mostly 300-1,500 Da.Most C-terminals contain aromatic amino acid(Phe,Trp and Tyr),Pro,Leu or Gly,and most N-terminals contain hydrophobic amino acid such as Leu,Ile,Val,Tyr and Ala.Peptides with high inhibitory activity which conform the structural characteristics above were selected from the collected grain-derived ACE inhibitory peptides for a full flexible molecular docking study to investigate the mode of interaction with inhibitory peptides and determine the key amino acid residues that affect the peptide activities.The simulation result of the full flexible molecular docking study showed that ACE inhibitory peptides could form hydrogen bond forces with the active pockets of angiotensin-converting enzyme molecules,and there are strong hydrophobic and hydrophilic forces between them.Therefore,hydrogen bond and hydrophobic force are the main forces to maintain the combination of inhibitory peptides and angiotensin-converting enzymes.When Tyr,Pro or Phe appears at the C-terminus of a polypeptide,and Leu or Ile appears at the N-terminus at the same time,the polypeptide usually exhibits higher ACE inhibitory activity.