Virtual screening for angiotensin I-converting enzyme inhibitory peptides from Phascolosoma esculenta

Abstract

Background

Many short peptides have proved to exhibit potential anti-hypertensive activity through the inhibition of the Angiotensin I-converting enzyme (ACE) activity and the regulation of blood pressure. However, the traditional experimental screening method for ACE inhibitory peptides is time consuming and costly, accompanied with the limitations as incomplete hydrolysis and peptides loss during purification process. Virtual methods with the aid of computer can break such bottle-neck of experimental work. In this study, an attempt was made to establish a library of di- and tri-peptides derived from proteins of Phascolosoma esculenta, a kind of seafood, through BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/pl/biopep), and to screen highly active ACE inhibitory peptides by molecular docking with the help of LibDock module of Discovery Studio 3.5 software.

Results

Two hundred and eighty four (284) di- and tri-peptides, derived from P. esculenta proteins after a virtual hydrolysis with pepsin, trypsin and a mixture of pepsin and trypsin, were predicted to possess ACE inhibitory activity, among which there are 99 ACE inhibitory peptides with estimated IC₅₀ less than 50 μM. Nine peptides were synthesized for the comparison between the estimated and the experimentally determined IC₅₀. The results indicated that errors between the estimated and measured log(1/IC₅₀) are all less than 1.0 unit.

Conclusions

Virtual method for peptide library construction and ACE inhibitory peptides screening efficiently demonstrated that P. esculenta proteins are prospect resource for food-origin ACE inhibitory peptide.

Keywords

Virtual screening / Angiotensin I-converting enzyme (ACE) / ACE inhibitory peptide / Phascolosoma esculenta

References

[1] Jung WK, Mendis E, Je JY, Park PJ, Son BW, Kim HC, Choi YK, Kim SK. Angiotensin I-converting enzyme inhibitory peptide from yellowfin sole (Limanda aspera) frame protein and its antihypertensive effect in spontaneously hypertensive rats. Food Chem, 2006, 94 1 26-32.

[2] Silva DG, Freitas MP, da Cunha EFF, Ramalho TC, Nunes CA. Rational design of small modified peptides as ACE inhibitors. Med Chem Comm, 2012, 3 10 1290-1293.

[3] Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet, 2005, 365 9455 217-223.

[4] Li GH, Le GW, Shi YH, Shrestha S. Angiotensin I-converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects. Nutr Res, 2004, 24 7 469-486.

[5] Guang C, Phillips RD. Plant food-derived angiotensin I converting enzyme inhibitory peptides. J Agric Food Chem, 2009, 57 12 5113-5120.

[6] De Leo F, Panarese S, Gallerani R, Ceci L. Angiotensin converting enzyme (ACE) inhibitory peptides: production and implementation of functional food. Curr Pharm Des, 2009, 15 31 3622-3643.

[7] Iroyukifujita H, Eiichiyokoyama K, Yoshikawa M. Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins. J Food Sci, 2000, 65 4 564-569.

[8] Reneland R, Lithell H. Angiotensin-converting enzyme in human skeletal muscle. A simple in vitro assay of activity in needle biopsy specimens. Scand J Clin Lab Investig, 1994, 54 2 105-111.

[9] Hartl FU. Molecular chaperones in cellular protein folding. Nature, 1996, 381: 571-580.

[10] Sturrock E, Natesh R, Van Rooyen J, Acharya K. Structure of angiotensin I-converting enzyme. Cell Mol Life Sci, 2004, 61: 2677-2686.

[11] Lin L, Lv S, Li B. Angiotensin-I-converting enzyme (ACE)-inhibitory and antihypertensive properties of squid skin gelatin hydrolysates. Food Chem, 2012, 131 1 225-230.

[12] Sweitzer NK. What is an angiotensin converting enzyme inhibitor?. Circulation, 2003, 108 3 e16-e18.

[13] Antonios TF, MacGregor GA. Angiotensin converting enzyme inhibitors in hypertension: potential problems. J Hypertens, 1995, 13: S11-S16.

[14] Ondetti MA, Williams NJ, Sabo E, Pluscec J, Weaver ER, Kocy O. Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry, 1971, 10 22 4033-4039.

[15] Abubakar A, Saito T, Kitazawa H, Kawai Y, Itoh T. Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J Dairy Sci, 1998, 81 12 3131-3138.

[16] Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci, 1995, 78 4 777-783.

[17] Andújar-Sánchez M, Cámara-Artigas A, Jara-Pérez V. A calorimetric study of the binding of lisinopril, enalaprilat and captopril to angiotensin-converting enzyme. Biophys Chem, 2004, 111 2 183-189.

[18] Wu J, Ding X. Hypotensive and physiological effect of angiotensin converting enzyme inhibitory peptides derived from soy protein on spontaneously hypertensive rats. J Agric Food Chem, 2001, 49 1 501-506.

[19] Mallikarjun Gouda K, Gowda LR, Rao AA, Prakash V. Angiotensin I-converting enzyme inhibitory peptide derived from glycinin, the 11S globulin of soybean (Glycine max). J Agric Food Chem, 2006, 54 13 4568-4573.

[20] Suh H, Whang J, Lee H. A peptide from corn gluten hydrolysate that is inhibitory toward angiotensin I converting enzyme. Biotechnol Lett, 1999, 21 12 1055-1058.

[21] Vercruysse L, Van Camp J, Morel N, Rougé P, Herregods G, Smagghe G. Ala-Val-Phe and Val-Phe: ACE inhibitory peptides derived from insect protein with antihypertensive activity in spontaneously hypertensive rats. Peptides, 2010, 31 3 482-488.

[22] Quist EE, Phillips RD, Saalia FK. Angiotensin converting enzyme inhibitory activity of proteolytic digests of peanut (Arachis hypogaea L.) flour. LWT-Food Sci Technol, 2009, 42 3 694-699.

[23] Majumder K, Wu J. Angiotensin I converting enzyme inhibitory peptides from simulated in vitro gastrointestinal digestion of cooked eggs. J Agric Food Chem, 2009, 57 2 471-477.

[24] Wang C, Tian J, Wang Q. ACE inhibitory and antihypertensive properties of apricot almond meal hydrolysate. Eur Food Res Technol, 2011, 232 3 549-556.

[25] Vermeirssen V, Camp JV, Verstraete W. Bioavailability of angiotensin I converting enzyme inhibitory peptides. Br J Nutr, 2004, 92 03 357-366.

[26] Jimsheena V, Gowda LR. Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from arachin by simulated gastric digestion. Food Chem, 2011, 125 2 561-569.

[27] Seppo L, Jauhiainen T, Poussa T, Korpela R. A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutri, 2003, 77 2 326-330.

[28] Mathews D, Adibi S. Peptide absorption. Gastroenterology, 1976, 71 1 151.

[29] Wu J, Aluko RE, Nakai S. Structural requirements of angiotensin I-converting enzyme inhibitory peptides: quantitative structure-activity relationship study of di-and tripeptides. J Agric Food Chem, 2006, 54 3 732-738.

[30] Wijesekara I, Qian ZJ, Ryu B, Ngo DH, Kim SK. Purification and identification of antihypertensive peptides from seaweed pipefish (Syngnathus schlegeli) muscle protein hydrolysate. Food Res Int, 2011, 44 3 703-707.

[31] Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res, 2000, 28 1 235-242.

[32] Pripp AH. Docking and virtual screening of ACE inhibitory dipeptides. Eur Food Res Technol, 2007, 225 3–4 589-592.

[33] Su X, Du L, Li Y, Li T, Li D, Wang M, He J. Production of recombinant protein and polyclonal mouse antiserum for ferritin from Sipuncula Phascolosoma esculenta. Fish Shellfish Immunol, 2009, 27 3 466-468.

[34] Du L, Fang M, Wu H, Xie J, Wu Y, Li P, Zhang D, Huang Z, Xia Y, Zhou L. A novel angiotensin I-converting enzyme inhibitory peptide from Phascolosoma esculenta water-soluble protein hydrolysate. J Funct Foods, 2013, 5 1 475-483.

[35] Wu H, Liu Y, Guo M, Xie J, Jiang X. A virtual screening method for inhibitory peptides of angiotensin I converting enzyme. J Food Sci, 2014, 79: C1635-C1642.

[36] Kerwin SM. ChemBioOffice Ultra 2010 suite. J Am Chem Soc, 2010, 132 7 2466-2467.

[37] Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem, 1983, 4 2 187-217.

[38] Cushman D, Cheung H. Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol, 1971, 20 7 1637-1648.

[39] Iwaniak A, Minkiewicz P, Darewicz M. Food-originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction. Compr Rev Food Sci Food Safety, 2014, 13 2 114-134.

[40] Kobayashi Y, Yamauchi T, Katsuda T, Yamaji H, Katoh S. Angiotensin-I converting enzyme (ACE) inhibitory mechanism of tripeptides containing aromatic residues. J Biosci Bioeng, 2008, 106 3 310-312.

[41] Sagardia I, Roa-Ureta RH, Bald C. A new QSAR model, for angiotensin I-converting enzyme inhibitory oligopeptides. Food Chem, 2013, 136 3 1370-1376.

[42] Wu J, Aluko RE, Nakai S. Structural requirements of angiotensin I-converting enzyme inhibitory peptides: quantitative structure-activity relationship modeling of peptides containing 4-10 amino acid residues. QSAR Combinat Sci, 2006, 25 10 873-880.

[43] Pripp AH, Isaksson T, Stepaniak L, Søhaug T. Quantitative structure-activity relationship modelling of ACE-inhibitory peptides derived from milk proteins. Eur Food Res Technol, 2004, 219 6 579-583.

[44] Kim SY, Je JY, Kim SK. Purification and characterization of antioxidant peptide from hoki (Johnius belengerii) frame protein by gastrointestinal digestion. J Nutr Biochem, 2007, 18 1 31-38.

[45] Ruiz-Giménez P, Marcos JF, Torregrosa G, Lahoz A, Fernández-Musoles R, Valles S, Alborch E, Manzanares P, Salom JB. Novel antihypertensive hexa- and heptapeptides with ACE-inhibiting properties: from the in vitro ACE assay to the spontaneously hypertensive rat. Peptides, 2011, 32 7 1431-1438.

[46] Kapel R, Rahhou E, Lecouturier D, Guillochon D, Dhulster P. Characterization of an antihypertensive peptide from an Alfalfa white protein hydrolysate produced by a continuous enzymatic membrane reactor. Process Biochem, 2006, 41 9 1961-1966.

[47] Pripp AH. Initial proteolysis of milk proteins and its effect on formation of ACE-inhibitory peptides during gastrointestinal proteolysis: a bioinformatic, in silico, approach. Eur Food Res Technol, 2005, 221 5 712-716.

[48] Wu J, Aluko RE. Quantitative structure-activity relationship study of bitter di-and tri-peptides including relationship with angiotensin I-converting enzyme inhibitory activity. J Pept Sci, 2007, 13 1 63-69.