Studies On Structural-functional Relationship Of ACE Inhibitory Peptides From Pistachio And In Silico Mechanism Of Peptides Binding With ACE

Pistachio (Pistacia vera L.) is a nutritional food and rich in protein, oil, vitamins and minerals, consuming around the world. Angiotensin I-converting enzyme (ACE), a membrane anchored dipeptidyl peptidase that hydrolyses angiotensin I to the potent vasoconstrictor angiotensin Ⅱ and by abrogating a potent vasodilator bradykinin to its inactive fragments play a key role in the blood pressure homeostasis. In this work, we separated and identified ACE inhibitory peptides from Pistachio. Also the structural-functional relationship and inhibitory mechanism of peptides were explored. The work could be divided into next four sections.The first section, the ACE inhibitory activity of hydrolysates from pistachio’s (Pistacia vera L.) kernel successively hydrolyzed by pepsin and trypsin as well as single trypsin were studied. Results indicated that the hydrolysates presented in vitro ACE inhibitory activity were IC500.8mg/mL, and in vivo antihypertensive activity which decreased around22mmHg in SBP and16mmHg in DBP at4h after the oral administration. Then the hydrolysis condition of trypsin hydrolysis method was optimized by using response surface experiments.The second section, six ACE inhibitory peptides WPF, GNPR, VFPR, GEPF, VPEGLNSWPF and KAKP were purified and identified by using ultrafiltration (UF), sephadex gel, reversed-phase high-performance liquid chromatography (RP-HPLC) and tandem mass spectrum, of which the lowest IC50was7.23μM.The third section, the structural-functional relationship of the ACE inhibitory peptides was carried out by interchanging the C-terminal amino acid to internal site. The ACE inhibitory activities of such new peptides were either enhanced in a range of1.5to74times or greatly decreased190times. The mechanism of activity changes was also confirmed by the simulation of molecular docking.