title: Characterization of ACE inhibitory peptides from Mactra veneriformis hydrolysate by nano-liquid chromatography electrospray ionization mass spectrometry (Nano-LC-ESI-MS) and molecular docking.
abstract: Food-derived bioactive compounds are gaining increasing significance in life sciences. In the present study, we identified angiotensin I-converting enzyme (ACE)-inhibitory peptides from Mactra veneriformis hydrolysate using a nano-LC-MS/MS method. Mactra veneriformis hydrolysate was first separated into four fractions (F1-F4) based on molecular weight by ultrafiltration. The fraction with molecular weight lower than 1 kDa (F1) showed the highest ACE inhibitory activity. F1 was then analyzed by a high throughput nano-LC-MS/MS method and sequences of peptides in F1 were calculated accordingly. The 27 peptides identified as above were chemically synthesized and tested for ACE-inhibitory activity. The hexapeptide VVCVPW showed the highest potency with an IC50 value of 4.07 μM. We then investigated the interaction mechanism between the six most potent peptides and ACE by molecular docking. Our docking results suggested that the ACE inhibitory peptides bind to ACE via interactions with His383, His387, and Glu411 residues. Particularly, similar to the thiol group of captopril, the cysteine thiol group of the most potent peptide VVCVPW may play a key role in the binding of this peptide to the ACE active site.
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. cpulr@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. hanziying@163.com.
authors.forename: Yunhan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: China Pharmaceutical University, Nanjing, Jiangsu 210009, China. chenjiao208@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. whao5795@vip.sina.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. pa.only@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. wxzatnj@sina.com.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. 993wlc@njutcm.edu.cn.
authors.forename: Lingchong
authors.initials: L
authors.lastname: Wang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D049872:Bivalvia / Q000737:chemistry*; D002853:Chromatography, Liquid; D062105:Molecular Docking Simulation; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry; D011492:Protein Hydrolysates / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; D011492:Protein Hydrolysates; D007703:Peptidyl-Dipeptidase A