Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates

Abstract

Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes.

Inhibition of dipeptidyl peptidase IV by enzymatic hydrolysates derived from primary and secondary whey of fresh and Oaxaca cheeses

“…For example, pepsin hydrolysates of α‐lactalbumin and bovine milk whey have IC 50 s of ~36–50 μg/mL and 70 μg/mL, respectively (Lacroix and Li‐Chan ; Nongonierma and FitzGerald, ), whereas a β‐lactoglobulin digested with trypsin has IC 50 s of 174 μM (Uchida et al ). Also, mare’s milk whey digested with papain for 4 h can generate peptide fragments with IC 50 of 180 μg/mL (Song et al ), which is 35% higher than the result obtained in this study (92.8670 μg/mL). Isolated milk serum hydrolysed with pepsin showed an IC 50 of 75 μg/mL (Lacroix and Li‐Chan ), an activity which is ~57% lower than that observed in this study.…”

“…Once hydrolysates with high DPP‐IV inhibitory action have been identified, it is important to detect what peptides are responsible for such activity. For example, in the mare’s milk hydrolysates two oligopeptides with primary sequences of Asn‐Leu‐Glu‐Ile‐Ile‐Leu‐Arg and Thr‐Gln‐Met‐Val‐Asp‐Glu‐Glu‐Ile‐Met‐Glu‐Lys‐Phe‐Arg were identified, corresponding to β‐lactoglobulin F1 (71–77) and β‐lactoglobulin F1 (143–155), with IC 50 of 86.34 and 69.84 μM, respectively (Song et al ). Lacroix and Li‐Chan () reported that Leu‐Lys‐Pro‐Thr‐Pro‐Glu‐Gly‐Asp‐Leu and Leu‐Lys‐Pro‐Thr‐Pro‐Glu‐Gly‐Asp‐Leu‐Glu‐Ile‐Leu obtained from β‐lactoglobulin fraction were the most effective DPP‐IV inhibitors with activities of 45 and 57 μM, respectively.…”

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

“…Considering the peptide sequences provided in Table 3 , most of them were composed of the following amino acids: Pro, Phe, Gly, Leu, and Arg. According to Song et al [ 47 ], the first three residues were found as peptide constituents characteristic of DPP-IV inhibitors, whereas Arg (among others) can be found in the peptides acting as ACE inhibitors [ 48 ].…”

“…Considering the peptide sequences provided in Table 3, most of them were composed of the following amino acids: Pro, Phe, Gly, Leu, and Arg. According to Song et al [47], the first three residues were found as peptide constituents characteristic of DPP-IV inhibitors, whereas Arg (among others) can be found in the peptides acting as ACE inhibitors [48]. 1 ACE i and DPP-IV i -angiotensin converting enzyme inhibitor and dipeptidyl peptidase IV inhibitor, respectively, 2 Pep-pepsin, 3 bold font-collagen hydrolysate source in which the peptide was identified more than once; 4 T-trypsin.…”

Discovery of Food-Derived Dipeptidyl Peptidase IV Inhibitory Peptides: A Review

“…Combination of two or three of the above chromatography methods should achieve peptide purification. Song et al, Huang et al, and Ji et al combined gel filtration chromatography and C 18 chromatography to purify DPP-IV inhibitory peptides [37,38,39]. Harnedy et al used a C 18 matrix solid-phase extraction (SPE) column followed by Semipreparative reversed-phase high performance liquid chromatography (SP RP-HPLC) to obtain three purified DPP-IV inhibitory peptides [40].…”