{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:23:55Z","timestamp":1791577435850,"version":"4.3.4"},"reference-count":87,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","award":["592148"],"award-info":[{"award-number":["592148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, we characterized three novel peptides derived from the 19 kDa \u03b1-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed \u03b1-helical structures and had positive and negative electrostatic potential surfaces (range of \u22121 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (\u22640.05%), cell penetration (10\u201333%) and antioxidant activities (9\u201312.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed \u03b1-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa \u03b1-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.<\/jats:p>","DOI":"10.3390\/molecules25225405","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T06:23:52Z","timestamp":1605767032000},"page":"5405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["In Silico Analysis and In Vitro Characterization of the Bioactive Profile of Three Novel Peptides Identified from 19 kDa \u03b1-Zein Sequences of Maize"],"prefix":"10.3390","volume":"25","author":[{"given":"Jorge L.","family":"D\u00edaz-G\u00f3mez","sequence":"first","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, 64849 Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-3991","authenticated-orcid":false,"given":"Ines","family":"Neundorf","sequence":"additional","affiliation":[{"name":"Department f\u00fcr Chemie, Institut f\u00fcr Biochemie, Universit\u00e4t zu K\u00f6ln, D-50674 K\u00f6ln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Margarita","family":"L\u00f3pez-Castillo","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, 64849 Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Castorena-Torres","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Tecnologico de Monterrey, 64710 Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio O.","family":"Serna-Sald\u00edvar","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, 64849 Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-957X","authenticated-orcid":false,"given":"Silverio","family":"Garc\u00eda-Lara","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, 64849 Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/fqs\/fyx006","article-title":"Bioactive peptides: A review","volume":"1","year":"2017","journal-title":"Food Qual. Saf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12929-017-0328-x","article-title":"Evaluation of the use of therapeutic peptides for cancer treatment","volume":"24","author":"Marqus","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cbdd.12055","article-title":"The future of peptide-based drugs","volume":"81","author":"Craik","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_4","first-page":"1","article-title":"Anti-cancer activity of maize bioactive peptides","volume":"5","year":"2017","journal-title":"Front. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Borrelli, A., Tornesello, A.L., Tornesello, M.L., and Buonaguro, F.M. (2018). Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules, 23.","DOI":"10.3390\/molecules23020295"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1476-5381.2009.00057.x","article-title":"Twenty years of cell-penetrating peptides: From molecular mechanisms to therapeutics","volume":"157","author":"Heitz","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4103\/0973-7847.70902","article-title":"Free radicals, antioxidants and functional foods: Impact on human health","volume":"4","author":"Lobo","year":"2010","journal-title":"Pharmacogn. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Daliri, E.B., Oh, D.H., and Lee, B.H. (2017). Bioactive peptides. Foods, 6.","DOI":"10.3390\/foods6050032"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.mpmed.2018.06.009","article-title":"Hypertension","volume":"46","author":"Bhagani","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/1541-4337.12411","article-title":"A comprehensive review of corn protein-derived bioactive peptides: Production, characterization, bioactivities, and transport pathways","volume":"18","author":"Zhu","year":"2019","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.3762\/bjoc.10.118","article-title":"Automated solid-phase peptide synthesis to obtain therapeutic peptides","volume":"10","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1080\/10408398.2017.1319795","article-title":"Current trends and perspectives of bioactive peptides","volume":"58","author":"Daliri","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chakrabarti, S., Guha, S., and Majumder, K. (2018). Food-derived bioactive peptides in human health: Challenges and opportunities. Nutrients, 10.","DOI":"10.3390\/nu10111738"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jprot.2014.03.044","article-title":"Preventive and therapeutic potential of peptides from cereals against cancer","volume":"111","author":"Winkler","year":"2014","journal-title":"J. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/j.1745-4514.2010.00451.x","article-title":"Induction of apoptosis in cervix neoplasms hela cells by a rapeseed peptide hydrolysate fraction","volume":"35","author":"Xue","year":"2011","journal-title":"J. Food Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jff.2017.04.015","article-title":"Antiproliferative effect of peptide fractions isolated from a quality protein maize, a white hybrid maize, and their derived peptides on hepatocarcinoma human HepG2 cells","volume":"34","author":"Aguilar","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_17","first-page":"255","article-title":"A peptide fraction from germinated soybean protein down-regulates PTTG1 and TOP2A mRNA expression, inducing apoptosis in cervical cancer cells","volume":"9","year":"2012","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.foodchem.2011.03.127","article-title":"Antihypertensive effect of corn peptides, produced by a continuous production in enzymatic membrane reactor, in spontaneously hypertensive rats","volume":"128","author":"Huang","year":"2011","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6059","DOI":"10.1021\/jf060632q","article-title":"Antioxidant activity of zein hydrolysates in a liposome system and the possible mode of action","volume":"54","author":"Kong","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1021\/acs.jafc.7b04562","article-title":"Identification of new anti-inflammatory peptides from zein hydrolysate after simulated gastrointestinal digestion and transport in Caco-2 cells","volume":"66","author":"Liang","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C2174","DOI":"10.1111\/1750-3841.12686","article-title":"Evaluation of antioxidant activities of zein protein fractions","volume":"79","author":"Tang","year":"2014","journal-title":"J. Food Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1039\/C5FO00815H","article-title":"Isolation and identification of a novel peptide from zein with antioxidant and antihypertensive activities","volume":"6","author":"Wang","year":"2015","journal-title":"Food Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.fct.2012.09.038","article-title":"Apoptosis in human hepatoma HepG2 cells induced by corn peptides and its anti-tumor efficacy in H22 tumor bearing mice","volume":"51","author":"Li","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.foodchem.2016.02.119","article-title":"Preparation of antioxidative corn protein hydrolysates, purification and evaluation of three novel corn antioxidant peptides","volume":"204","author":"Jin","year":"2016","journal-title":"Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.procbio.2014.07.002","article-title":"Preparation of active corn peptides from zein through double enzymes immobilized with calcium alginate-chitosan beads","volume":"49","author":"Wang","year":"2014","journal-title":"Process Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.foodchem.2015.04.092","article-title":"Antioxidant peptides from corn gluten meal: Orthogonal design evaluation","volume":"187","author":"Zhou","year":"2015","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.jff.2013.08.013","article-title":"Purification and identification of antioxidant peptides from corn gluten meal","volume":"5","author":"Zhuang","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"D\u00edaz-G\u00f3mez, J.L., Ort\u00edz-Mart\u00ednez, M., Aguilar, O., Garc\u00eda-Lara, S., and Castorena-Torres, F. (2018). Antioxidant activity of zein hydrolysates from Zea species and their cytotoxic effects in a hepatic cell culture. Molecules, 23.","DOI":"10.3390\/molecules23020312"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.chroma.2013.02.015","article-title":"Development of a high-performance liquid chromatography\u2013electrospray ionization-quadrupole-time-of-flight-mass spectrometry methodology for the determination of three highly antihypertensive peptides in maize crops","volume":"1285","author":"Puchalska","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.fbp.2013.06.003","article-title":"Ultrasonic pretreatment of corn gluten meal proteins and neutrase: Effect on protein conformation and preparation of ACE (angiotensin converting enzyme) inhibitory peptides","volume":"91","author":"Zhou","year":"2013","journal-title":"Food Bioprod. Process."},{"key":"ref_31","unstructured":"(2019, September 01). Innovagen AB Peptide Property Calculator. Available online: https:\/\/pepcalc.com\/."},{"key":"ref_32","unstructured":"(2020, November 01). Cell Penetrating Peptides. Available online: http:\/\/bioware.ucd.ie\/~compass\/biowareweb\/Server_pages\/cpppred.php."},{"key":"ref_33","unstructured":"(2020, November 01). A Sequence-Based Tool for Identifying Anticancer Peptides. Available online: http:\/\/lin-group.cn\/server\/iACP."},{"key":"ref_34","unstructured":"(2020, November 01). Antioxidant and Angiotensin-Converting Enzyme (ACE) Inhibition. Available online: http:\/\/www.uwm.edu.pl\/biochemia\/index.php\/en\/bi."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3390\/ph2020049","article-title":"Fusion of a short HA2-derived peptide sequence to cell-penetrating peptides improves cytosolic uptake, but enhances cytotoxic activity","volume":"2","author":"Neundorf","year":"2009","journal-title":"Pharmaceuticals"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jconrel.2018.10.029","article-title":"Bifunctional peptide hybrids targeting the matrix of mitochondria","volume":"291","author":"Klimpel","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Avci, F.G., Akbulut, B.S., and Ozkirimli, E. (2018). Membrane active peptides and their biophysical characterization. Biomolecules, 8.","DOI":"10.20944\/preprints201807.0008.v1"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fangh\u00e4nel, S., Wadhwani, P., Strandberg, E., Verdurmen, W.P.R., B\u00fcrck, J., Ehni, S., Mykhailiuk, P.K., Afonin, S., Gerthsen, D., and Komarov, I.V. (2014). Structure analysis and conformational transitions of the cell penetrating peptide transportan 10 in the membrane-bound state. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099653"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1021\/jf058135h","article-title":"Structural characterization of \u03b1-zein","volume":"54","author":"Momany","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9984","DOI":"10.1016\/S0021-9258(18)33974-7","article-title":"A structural model for maize zein proteins","volume":"257","author":"Argos","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.bbapap.2006.04.002","article-title":"Effect of temperature and pH on the secondary structure and processes of oligomerization of 19 kDa alpha-zein","volume":"1764","author":"Cabra","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.3762\/bjoc.14.116","article-title":"Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions","volume":"14","author":"Gronewold","year":"2018","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13003","DOI":"10.1073\/pnas.97.24.13003","article-title":"The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters","volume":"97","author":"Wender","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbcan.2011.07.006","article-title":"Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer","volume":"1816","author":"Bolhassani","year":"2011","journal-title":"Biochim. Biophys. Acta\u2014Rev. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Reinhardt, A., Thomas, I., Schmauck, J., Giernoth, R., Schulze, A., and Neundorf, I. (2018). Electron beam immobilization of novel antimicrobial, short peptide motifs leads to membrane surfaces with promising antibacterial properties. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9010021"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/cmdc.201600498","article-title":"Characterization of a cell-penetrating peptide with potential anticancer activity","volume":"12","author":"Gronewold","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.foodres.2014.09.023","article-title":"Antioxidant properties of peptide fractions from tuna dark muscle protein by-product hydrolysate produced by membrane fractionation process","volume":"65","author":"Saidi","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jff.2018.05.034","article-title":"Biochemical requirements of bioactive peptides for nutraceutical efficacy","volume":"47","author":"Gianfranceschi","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0926-6690(00)00064-9","article-title":"Zein: The industrial protein from corn","volume":"13","author":"Shukla","year":"2001","journal-title":"Ind. Crops Prod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.foodchem.2015.02.147","article-title":"Determination of reducing power and metal chelating ability of antioxidant peptides: Revisited methods","volume":"183","author":"Kessler","year":"2015","journal-title":"Food Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.jff.2013.11.005","article-title":"Structural and functional characterization of hemp seed (Cannabis sativa L.) protein-derived antioxidant and antihypertensive peptides","volume":"6","author":"Girgih","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.drudis.2012.03.002","article-title":"Cell-penetrating peptides: Classes, origin, and current landscape","volume":"17","author":"Milletti","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.biopha.2018.09.097","article-title":"Cell penetrating peptides: A concise review with emphasis on biomedical applications","volume":"108","author":"Derakhshankhah","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_54","unstructured":"Cooper, G.M. (2020, September 07). Endocytosis, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK9831\/."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.foodchem.2012.05.063","article-title":"Production and functional characterisation of antioxidative hydrolysates from corn protein via enzymatic hydrolysis and ultrafiltration","volume":"135","author":"Zhou","year":"2012","journal-title":"Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jcs.2017.05.021","article-title":"Antioxidant activity and characterization of protein fractions and hydrolysates from normal and quality protein maize kernels","volume":"76","year":"2017","journal-title":"J. Cereal Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"155","DOI":"10.18633\/biotecnia.v22i2.1257","article-title":"Evaluation of the in vitro and in vivo antihypertensive effect and antioxidant activity of blue corn hydrolysates derived from wet-milling","volume":"22","year":"2020","journal-title":"Biotecnia"},{"key":"ref_58","first-page":"415","article-title":"Antioxidative activities and peptide compositions of corn protein hydrolysates pretreated by different ultrasonic methods","volume":"3","author":"Huang","year":"2015","journal-title":"J. Food Nutr. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.foodres.2016.10.023","article-title":"Intracellular ROS scavenging and antioxidant enzyme regulating capacities of corn gluten meal-derived antioxidant peptides in HepG2 cells","volume":"90","author":"Wang","year":"2016","journal-title":"Food Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.1021\/jf0705670","article-title":"Peptide with angiotensin I-converting enzyme inhibitory activity from hydrolyzed corn gluten meal","volume":"55","author":"Yang","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.foodchem.2010.06.099","article-title":"Pilot-scale production of low molecular weight peptides from corn wet milling byproducts and the antihypertensive effects in vivo and in vitro","volume":"124","author":"Lin","year":"2011","journal-title":"Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1021\/jf072238d","article-title":"Angiotensin I converting enzyme-inhibitory peptides from commercial wet- and dry-milled corn germ","volume":"56","author":"Parris","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1271\/bbb.60.661","article-title":"Isolation from \u03b1-zein of thermolysin peptides with angiotensin I-converting enzyme inhibitory activity","volume":"60","author":"Yano","year":"1996","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"103584","DOI":"10.1016\/j.jff.2019.103584","article-title":"Production of ACE inhibitory peptides from corn germ meal by an enzymatic membrane reactor with a novel gradient diafiltration feeding working-mode and in vivo evaluation of antihypertensive effect","volume":"64","author":"Guo","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_65","first-page":"2763","article-title":"Angiotensin I-converting enzyme inhibitors derived from Ficus carica","volume":"53","author":"Maruyama","year":"1989","journal-title":"Agric. Biol. Chem."},{"key":"ref_66","first-page":"1313","article-title":"Structures and activity of angiotensin-converting enzyme inhibitors in an \u03b1-zein hydrolysate","volume":"55","author":"Miyoshi","year":"1991","journal-title":"Agric. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10126-001-0012-7","article-title":"Identification of antihypertensive peptides from peptic digest of two microalgae, Chlorella vulgaris and Spirulina platensis","volume":"3","author":"Suetsuna","year":"2001","journal-title":"Mar. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00216-008-1990-3","article-title":"Application of at-line two-dimensional liquid chromatography\u2013mass spectrometry for identification of small hydrophilic angiotensin I-inhibiting peptides in milk hydrolysates","volume":"391","author":"Janssen","year":"2008","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1671-2927(11)60026-6","article-title":"A novel angiotensin I converting enzyme inhibitory peptide from the milk casein: Virtual screening and docking studies","volume":"10","author":"Wang","year":"2011","journal-title":"Agric. Sci. China"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/jsfa.3264","article-title":"In vitro antioxidant activity of protein hydrolysates prepared from corn gluten meal","volume":"88","author":"Li","year":"2008","journal-title":"J. Sci. Food Agric."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1745-4514.2011.00613.x","article-title":"Ultrafiltration preparation of potent bioactive corn peptide as alcohol metabolism stimulator in vivo and study on its mechanism of action","volume":"37","author":"Yu","year":"2013","journal-title":"J. Food Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/qsar.200630005","article-title":"Structural requirements of angiotensin I-converting enzyme inhibitory peptides: Quantitative structure-activity relationship modeling of peptides containing 4-10 amino acid residues","volume":"25","author":"Wu","year":"2006","journal-title":"QSAR Comb. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.foodchem.2014.11.131","article-title":"Analyzing a dipeptide library to identify human dipeptidyl peptidase IV inhibitor","volume":"175","author":"Lan","year":"2015","journal-title":"Food Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI search and sequence analysis tools APIs in 2019","volume":"47","author":"Madeira","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014A multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: A worldwide hub of protein knowledge","volume":"47","author":"Bateman","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/btt518","article-title":"CPPpred: Prediction of cell penetrating peptides","volume":"29","author":"Holton","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16895","DOI":"10.18632\/oncotarget.7815","article-title":"iACP: A sequence-based tool for identifying anticancer peptides","volume":"7","author":"Chen","year":"2016","journal-title":"Oncotarget"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Minkiewicz, P., Iwaniak, A., and Darewicz, M. (2019). BIOPEP-UWM database of bioactive peptides: Current opportunities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235978"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1002\/prot.24065","article-title":"Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field","volume":"80","author":"Xu","year":"2012","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/prot.24179","article-title":"Toward optimal fragment generations for ab initio protein structure assembly","volume":"81","author":"Xu","year":"2013","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_83","unstructured":"DeLano, W.L. (2015). PhysiologyMOL Molecular Graphics System, Sch\u00f6dinger LLC. version 1.8."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"16279","DOI":"10.1038\/s41598-018-34684-1","article-title":"Design of a novel cell-permeable chimeric peptide to promote wound healing","volume":"8","author":"Horn","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Freshney, R.I. (2010). Culture of Animal Cells, John Wiley & Sons, Inc.. [6th ed.].","DOI":"10.1002\/9780470649367"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Alvarenga, E.C., Fonseca, M.C., Carvalho, C.C., Florentino, R.M., Fran\u00e7a, A., Matias, E., Guimar\u00e3es, P.B., Batista, C., Freire, V., and Carmona, A.K. (2016). Angiotensin converting enzyme regulates cell proliferation and migration. 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