title: Identification of novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides from meat proteins using in silico analysis.
abstract: Angiotensin-I-converting enzyme (ACE-I, EC 3.4.15.1), renin (EC 3.4.23.15), and dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) play key roles in the control of hypertension and the development of type-2 diabetes and other diseases associated with metabolic syndrome. The aim of this work was to utilize known in silico methodologies, peptide databases and software including ProtParam (http://web.expasy.org/protparam/), Basic Local Alignment Tool (BLAST), ExPASy PeptideCutter (http://web.expasy.org/peptide_cutter/) and BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/pl/biopep) to assess the release of potentially bioactive DPP-IV, renin and ACE-I inhibitory peptides from bovine and porcine meat proteins including hemoglobin, collagen and serum albumin. These proteins were chosen as they are found commonly in meat by-products such as bone, blood and low-value meat cuts. In addition, the bioactivities of identified peptides were confirmed using chemical synthesis and in vitro bioassays. The concentration of peptide required to inhibit the activity of ACE-I and DPP-IV by 50% was determined for selected, active peptides. Novel ACE-I and DPP-IV inhibitory peptides were identified in this study using both in silico analysis and a literature search to streamline enzyme selection for peptide production. These novel peptides included the ACE-I inhibitory tri-peptide Ile-Ile-Tyr and the DPP-IV inhibitory tri-peptide Pro-Pro-Leu corresponding to sequences f (182-184) and f (326-328) of both porcine and bovine serum albumin which can be released following hydrolysis with the enzymes papain and pepsin, respectively. This work demonstrates that meat proteins are a suitable resource for the generation of bioactive peptides and further demonstrates the usefulness of in silico methodologies to streamline identification and generation of bioactive peptides.
authors.affiliation: Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, Dublin 15, Ireland.
authors.forename: Tomas
authors.initials: T
authors.lastname: Lafarga
authors.affiliation: Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Moorepark, Fermoy, Cork, Ireland.
authors.forename: Paula
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Teagasc, The Irish Agricultural and Food Development Authority, Food BioSciences Department, Ashtown, Dublin 15, Ireland. Electronic address: maria.hayes@teagasc.ie.
authors.forename: Maria
authors.initials: M
authors.lastname: Hayes
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000737:chemistry*; D003198:Computer Simulation; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000032:analysis* / Q000494:pharmacology; D004285:Dogs; D006454:Hemoglobins / Q000737:chemistry*; D008460:Meat / Q000032:analysis*; D009842:Oligopeptides / Q000032:analysis / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry*; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006454:Hemoglobins; D009842:Oligopeptides; D012709:Serum Albumin; D003094:Collagen; D018819:Dipeptidyl Peptidase 4
keywords: ACE-I; Blood peptides; DPP-IV; In silico analysis; Meat proteins; Metabolic syndrome