title: Novel whey-derived peptides with inhibitory effect against angiotensin-converting enzyme: in vitro effect and stability to gastrointestinal enzymes.
abstract: Whey protein concentrate (WPC) was subjected to enzymatic hydrolysis by proteases from the flowers of Cynara cardunculus, and the resulting angiotensin-converting enzyme (ACE)-inhibitory effect was monitored. The whole WPC hydrolysate exhibited an IC(50) value of 52.9 ± 2.9 μg/mL, whereas the associated peptide fraction with molecular weight below 3 kDa scored 23.6 ± 1.1 μg/mL. The latter fraction was submitted to RP-HPLC, and 6 fractions were resolved that exhibited ACE-inhibitory effects. Among the various peptides found, a total of 14 were identified via sequencing with an ion-trap mass spectrometer. Eleven of these peptides were synthesized de novo--to validate their ACE-inhibitory effect, and also to ascertain their stability when exposed to simulated gastrointestinal digestion. Among them, three novel, highly potent peptides were found, corresponding to α-lactalbumin f(16-26)--with the sequence KGYGGVSLPEW, α-lactalbumin f(97-104) with DKVGINYW, and β-lactoglobulin f(33-42) with DAQSAPLRVY; their IC(50) values were as low as 0.80 ± 0.1, 25.2 ± 1.0 and 13.0 ± 1.0 μg/mL, respectively. None of them remained stable in the presence of gastrointestinal enzymes: they were partially, or even totally hydrolyzed to smaller peptides--yet the observed ACE-inhibitory effects were not severely affected for two of those peptides.
authors.affiliation: CBQF/Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Dr. António Bernardino de Almeida, P-4200-072 Porto, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Tavares
authors.forename: Maria Del Mar
authors.initials: Mdel M
authors.lastname: Contreras
authors.forename: Manuela
authors.initials: M
authors.lastname: Amorim
authors.forename: Manuela
authors.initials: M
authors.lastname: Pintado
authors.forename: Isidra
authors.initials: I
authors.lastname: Recio
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Malcata
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000201:enzymology*; D008894:Milk Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000067816:Whey Proteins
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008894:Milk Proteins; D010455:Peptides; D000067816:Whey Proteins; D007703:Peptidyl-Dipeptidase A