Rapid Identification of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides from Ruditapes philippinarum Hydrolysate

Abstract

Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides were rapidly identified from Ruditapes philippinarum hydrolysate. The hydrolysate was fractionated by ethanol precipitation and preparative reverse phase high-performance liquid chromatography (RP-HPLC). The fraction which showed the highest DPP-IV inhibitory activity was then analyzed by a high-throughput nano-liquid chromatography electrospray ionization tandem mass spectrometry (nano-LC ESI-MS/MS) method, and the sequences of peptides were identified based on the MS/MS spectra against the Mollusca protein data from the UniProt database. In total, 50 peptides were identified. Furthermore, molecular docking was used to identify potential DPP-IV inhibitors from the identified peptides. Docking results suggested that four peptides: FAGDDAPR, LAPSTM, FAGDDAPRA, and FLMESH, could bind pockets of DPP-IV through hydrogen bonds, π-π bonds, and charge interactions. The four peptides were chemically synthesized and tested for DPP-IV inhibitory activity. The results showed that they possessed DPP-IV inhibitory activity with IC50 values of 168.72 μM, 140.82 μM, 393.30 μM, and >500 μM, respectively. These results indicate that R. philippinarum-derived peptides may have potential as functional food ingredients for the prevention of diabetes.

Assessment of the DPP‐IV inhibitory activity of a novel octapeptide derived from rapeseed using Caco‐2 cell monolayers and molecular docking analysis

“…Arg125 (Liu et al, 2017). Simultaneously, the Glu at the N-terminus of ELHQEEPL also formed these three amino acid interactions with F I G U R E 7 (a) and (b) are More 2D graphs for the information of interaction between the ELHQEEPL, HQEEP and DPP-IV residues, respectively DPP-IV.…”

Dipeptidyl Peptidase-IV Inhibitory Activity and Related Molecular Mechanism of Bovine α-Lactalbumin-Derived Peptides

“…As listed in Table 1, the peptide sequences of the F3-8 and F3-11 were Glu-Leu-Lys-Asp-Leu-Lys-Gly-Tyr (ELKDLKGY) and Ile-Leu-Asp-Lys-Val-Gly-Ile-Asn-Tyr (ILDKVGINY), respectively. Figure 4A showed the LC-MS/MS spectrum of single-charged ion with m/z 483.26996, which matched to sequence ELKDLKGY corresponding to bovine α-lactalbumin f (30)(31)(32)(33)(34)(35)(36)(37). Figure 4B showed the LC-MS/MS spectrum of single-charged ion with m/z 517.79901, which matched to sequence ILDKVGINY corresponding to bovine α-lactalbumin f (114-122).…”

Role of hydrophobicity in food peptide functionality and bioactivity

“…DPP-IV is a metabolic enzyme that selectively converts the incretin hormones, gastric inhibitory peptide and glucagon-like peptide-1, into their inactive forms, thereby largely influencing postprandial insulin release. Because of its detrimental activity towards postprandial glucose regulation, DPP-IV inhibitory drugs called gliptins have been developed as a therapeutic strategy for type 2 diabetes mellitus (Liu et al, 2017). DPP-IV contains a hydrophobic site S1 with Tyr631, Val656, Trp659, Tyr666 and Val711 residues, and a charged site S2 with Arg125, Glu205, Glu206, Phe357, Ser209 and Arg358 residues (Power et al, 2014).…”

“…DPP-IV contains a hydrophobic site S1 with Tyr631, Val656, Trp659, Tyr666 and Val711 residues, and a charged site S2 with Arg125, Glu205, Glu206, Phe357, Ser209 and Arg358 residues (Power et al, 2014). Several studies using bioinformatics, in vitro and animal models have demonstrated that food proteins contain DPP-IV inhibiting peptides within their primary structures (Liu et al, 2017;Udenigwe et al, 2013). These peptides can be released using methods such as enzymatic hydrolysis and fermentation.…”

“…In general, food-derived peptides were observed to interact with both the hydrophobic S1 and charged S2 pockets of DPP-IV. For instance, Liu et al, (2017) reported that DPP-IV inhibiting peptides LAPSTM (IC 50 140 µM), FAGDDAPR (IC 50 168 µM) and FAGDDAPRA (IC 50 393 µM) interacted with regions of the enzyme through H-bonding and π-π interactions. The presence of hydrophobic amino acids at the N-terminus of peptides is a peculiar feature of identified DPP-IV inhibiting peptides.…”