scholarly journals Application of a Combined Peptidomics and In Silico Approach for the Identification of Novel Dipeptidyl Peptidase-IV-Inhibitory Peptides in In Vitro Digested Pinto Bean Protein Extract

2021 ◽  
Vol 44 (1) ◽  
pp. 139-151
Author(s):  
Serena Martini ◽  
Alice Cattivelli ◽  
Angela Conte ◽  
Davide Tagliazucchi
Keyword(s):  
In Silico ◽  
Integrated Approach ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Protein Extract ◽  
Dpp Iv ◽  
Pinto Bean ◽  
Starting Point ◽  
Bean Protein

The conventional approach in bioactive peptides discovery, which includes extensive bioassay-guided fractionation and purification processes, is tedious, time-consuming and not always successful. The recently developed bioinformatics-driven in silico approach is rapid and cost-effective; however, it lacks an actual physiological significance. In this study a new integrated peptidomics and in silico method, which combines the advantages of the conventional and in silico approaches by using the pool of peptides identified in a food hydrolysate as the starting point for subsequent application of selected bioinformatics tools, has been developed. Pinto bean protein extract was in vitro digested and peptides were identified by peptidomics. The pool of obtained peptides was screened by in silico analysis and structure–activity relationship modelling. Three peptides (SIPR, SAPI and FVPH) were selected as potential inhibitors of the dipeptidyl-peptidase-IV (DPP-IV) enzyme by this integrated approach. In vitro bioactivity assay showed that all three peptides were able to inhibit DPP-IV with the tetra-peptide SAPI showing the highest activity (IC50 = 57.7 μmol/L). Indeed, a new possible characteristic of peptides (i.e., the presence of an S residue at the N-terminus) able to inhibit DPP-IV was proposed.

scholarly journals Quercetin and Coumarin Inhibit Dipeptidyl Peptidase-IV and Exhibits Antioxidant Properties: In Silico, In Vitro, Ex Vivo

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 207 ◽  
Author(s):  
Anand-Krishna Singh ◽  
Pankaj Kumar Patel ◽  
Komal Choudhary ◽  
Jaya Joshi ◽  
Dhananjay Yadav ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Ex Vivo ◽  
Antioxidant Properties ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Food Ingredients ◽  
Dpp Iv ◽  
In Silico Studies

Quercetin and coumarin, two naturally occurring phytochemicals of plant origin, are known to regulate hyperglycemia and oxidative stress. The present study was designed to evaluate the inhibitory activity of quercetin and coumarin on dipeptidyl peptidase-IV (DPP-IV) and their antioxidant potential. DPP-IV inhibition assays were performed, and evaluated IC50 values of diprotin A, quercetin, coumarin, and sitagliptin were found to be 0.653, 4.02, 54.83, and 5.49 nmol/mL, respectively. Furthermore, in silico studies such as the drug-likeliness and docking efficiency of quercetin and coumarin to the DPP-IV protein were performed; the ex vivo antiperoxidative potential of quercetin and coumarin were also evaluated. The results of the present study showed that the DPP-IV inhibitory potential of quercetin was slightly higher than that of sitagliptin. Virtual docking revealed the tight binding of quercetin with DPP-IV protein. Quercetin and coumarin reduced oxidative stress in vitro and ex vivo systems. We report for the first time that both compounds inhibited the DPP-IV along with antioxidant activity and thus may be use as function food ingredients in the prevention of diabetes.

scholarly journals 4-Hydroxyderricin Isolated from the Sap of Angelica keiskei Koidzumi: Evaluation of Its Inhibitory Activity towards Dipeptidyl Peptidase-IV

2019 ◽  
Vol 87 (4) ◽  
pp. 30
Author(s):  
Diah Lia Aulifa ◽  
I Ketut Adnyana ◽  
Jutti Levita ◽  
Sukrasno Sukrasno
Keyword(s):  
In Silico ◽  
In Vitro Study ◽  
Gradient Elution ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Inhibition Constant ◽  
Hydroxyl Group ◽  
Dpp Iv ◽  
Angelica Keiskei

Angelica keiskei sap is used as a blood-sugar reducer in Indonesia, however its molecular mechanism has not yet been explored. 4-hydroxyderricin (4-HD) is one of the major components extracted from A. keiskei sap. The aim of this work was to isolate 4-HD from the sap of A. keiskei planted in Lombok, Indonesia, and to study in silico and in vitro mechanisms against dipeptidyl peptidase-IV (DPP-IV). The dried sap was submitted to liquid–liquid extraction using solvents with different polarity. Further purification processing was conducted using gradient elution column chromatography. The isolated compound was a yellowish powder, m/z 339.2215 [M + H]+, which was confirmed as 4-HD. Sitagliptin, a DPP-IV inhibitor, was employed as the positive control for both the in silico and in vitro studies. It was indicated that 4-HD interacts with Glu206 and Phe357, important amino acid residues in the DPP-IV binding pocket. These interactions are similar to that of sitagliptin. The affinity of 4-HD (inhibition constant (Ki) = 3.99 μM) to DPP-IV is lower than that of sitagliptin (inhibition constant (Ki) = 0.17 μM). Furthermore, in vitro study showed that 4-HD inhibits DPP-IV (IC50 = 81.44 μM) weaker than for sitagliptin (IC50 = 0.87 μM). We concluded that 4- HD might have potential in inhibiting DPP-IV. However, by considering the polar interaction of sitagliptin with DPP-IV, a further structure modification of 4-HD, e.g., by introducing a polar moiety such as a hydroxyl group, might be needed to obtain stronger activity as a DPP-IV inhibitor.

scholarly journals Gliptins vs. Milk-derived Dipeptidyl-Peptidase IV Inhibiting Biopeptides: Physicochemical Characterization and Pharmacokinetic Profiling

Revista Vitae ◽  
2021 ◽  
Vol 28 (3) ◽  
Author(s):  
Jorge Andrés Barrero ◽  
Fabio Cabrera ◽  
Claudia Marcela Cruz
Keyword(s):  
Physicochemical Properties ◽  
In Silico ◽  
Physicochemical Characterization ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Synthetic Accessibility ◽  
Enhanced Solubility ◽  
Significant Difference

Background: Milk-derived biopeptides have reported in vitro dipeptidyl-peptidase IV (DPP-IV) inhibition, suggesting a glycemic-regulatory effect in Type 2 Diabetes Mellitus (T2DM). Nonetheless, the therapeutic application of these nutraceuticals is limited by the scarcity of knowledge regarding their pharmacokinetic profile. Objective: This study aimed to characterize and assess the pharmacokinetics of milk-derived biopeptides. Through an in silico comparative analysis with gliptins, we expected to identify enhanced properties in food-hydrolysates and suitable DPP-IV inhibiting peptides as candidates for T2DM therapy. Methods: A comparison between gliptins and biopeptides was conducted based on in silico evaluation of drug-likeness, physicochemical properties, pharmacokinetics, and synthetic accessibility. Suitable target proteins for gastrointestinal-absorbable biopeptides were determined as well. Data collection was performed on SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes, and BIOPEP-UWM platforms. Statistical analysis was carried out using a one-way ANOVA test. Results: Drug-likeness compliance showed no significant difference between gliptins and biopeptides (p>0.05) in three out of nine assessed rules, though gastrointestinal-absorbable biopeptides exhibited no significant difference with gliptins in five drug-likeness guidelines. The physicochemical evaluation revealed a significant difference (p<0.05) between both groups, with peptides exhibiting enhanced solubility, flexibility, and polarity. Nine out of thirty-six assessed biopeptides reported being likely gastrointestinal-absorbable molecules, from which six displayed ≥30% predicted bioavailability, two reported CYP450 interactions, and all were determined to be blood confined. Biopeptides showed a slightly lower clearance than gliptins yet counteracted by a significantly lower half-life. Moreover, synthetic accessibility scores indicated higher synthetic ease for biopeptides. In addition, absorbable bioactive peptides reported a considerable binding affinity to DPP-IV and Calpain-I. Conclusions: Compared to gliptins, gastrointestinal-absorbable biopeptides exhibit superior physicochemical properties (higher solubility, flexibility, and polarity), lesser CYP450 interactions, higher synthetic ease, and some reported an important affinity for DPP-IV and Calpain-I. Only a small fraction of milk-derived biopeptides are suitable drug-like compounds and feasible candidates for T2DM therapy; yet, testing their therapeutic potency remains subject to further studies.

scholarly journals Identification and characterisation of peptides from a boarfish (Capros aper) protein hydrolysate displaying in vitro dipeptidyl peptidase-IV (DPP-IV) inhibitory and insulinotropic activity

2020 ◽  
Vol 131 ◽  
pp. 108989 ◽  
Author(s):  
Pádraigín A. Harnedy-Rothwell ◽  
Chris M. McLaughlin ◽  
Martina B. O'Keeffe ◽  
Aurélien V. Le Gouic ◽  
Philip J. Allsopp ◽  
...  
Keyword(s):  
Protein Hydrolysate ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv

scholarly journals Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Po-Kai Huang ◽  
Shian-Ren Lin ◽  
Chia-Hsiang Chang ◽  
May-Jwan Tsai ◽  
Der-Nan Lee ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Blood Sugar ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
C2c12 Cells ◽  
Surface Glycoprotein ◽  
Dpp Iv ◽  
Natural Phenolic Compounds

Abstract Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.

scholarly journals Dipeptidyl-Peptidase IV Converts Intact B-Type Natriuretic Peptide into Its des-SerPro Form

2006 ◽  
Vol 52 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Inger Brandt ◽  
Anne-Marie Lambeir ◽  
Jean-Marie Ketelslegers ◽  
Marc Vanderheyden ◽  
Simon Scharpé ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Ex Vivo ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Amino Terminal ◽  
Dpp Iv

Abstract Background: Analysis of plasma B-type natriuretic peptide (BNP) has suggested the in vivo formation of a truncated form, BNP (3–32), also called des-SerPro-BNP. The objectives of this study were to investigate (a) whether BNP and other natriuretic peptides are truncated by dipeptidyl-peptidase IV (DPP IV/CD26; EC 3.4.14.5) and (b) whether this truncation affects the susceptibility to cleavage by neutral endopeptidase (NEP; EC 3.4.24.11). Methods: Human BNP (1–32), A-type natriuretic peptide 1–28 (ANP 1–28), and related peptides were incubated with purified DPP IV and with human plasma. In addition, BNP (1–32), BNP (3–32), and ANP (1–28) were subjected to hydrolysis by NEP. Cleavage products were analyzed by mass spectrometry. Results: BNP (1–32) was cleaved by purified DPP IV with a specificity constant of 0.37 × 106 L · mol−1 · s−1. The DPP IV activity in EDTA-plasma was able to truncate BNP (1–32) ex vivo. Addition of Vildagliptin, a specific DPP IV inhibitor, prevented this truncation in a concentration-dependent manner. Under in vitro circumstances in which ANP was hydrolyzed extensively, BNP (1–32) and BNP (3–32) were very resistant to NEP-mediated cleavage. Conclusions: DPP IV cleaves BNP (1–32) with an efficiency higher than or comparable to several known in vivo substrates of the enzyme. Even after loss of the amino-terminal dipeptide, BNP remains highly resistant to cleavage by NEP.

scholarly journals Quinoa (Chenopodium quinoa Willd.) protein hydrolysates with in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant properties

2015 ◽  
Vol 65 ◽  
pp. 112-118 ◽  
Author(s):  
Alice B. Nongonierma ◽  
Solène Le Maux ◽  
Cécile Dubrulle ◽  
Chloé Barre ◽  
Richard J. FitzGerald
Keyword(s):  
Antioxidant Properties ◽  
Chenopodium Quinoa ◽  
Dipeptidyl Peptidase ◽  
Protein Hydrolysates ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv

scholarly journals Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides fromβ-Lactoglobulin Secreted byLactococcus lactis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Suguru Shigemori ◽  
Kazushi Oshiro ◽  
Pengfei Wang ◽  
Yoshinari Yamamoto ◽  
Yeqin Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Expression System ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Delivery Vehicle ◽  
Dpp Iv

Previous studies showed that hydrolysates ofβ-lactoglobulin (BLG) prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV) activityin vitro. In this study, we developed a BLG-secretingLactococcus lactisstrain as a delivery vehicle andin situexpression system. Interestingly, trypsin-digested recombinant BLG fromL. lactisinhibited DPP-IV activity, suggesting that BLG-secretingL. lactismay be useful in the treatment of type 2 diabetes mellitus.

scholarly journals A Novel Dipeptidyl Peptidase IV Inhibitory Tea Peptide Improves Pancreatic β-Cell Function and Reduces α-Cell Proliferation in Streptozotocin-Induced Diabetic Mice

2019 ◽  
Vol 20 (2) ◽  
pp. 322 ◽  
Author(s):  
Yating Lu ◽  
Peng Lu ◽  
Yu Wang ◽  
Xiaodong Fang ◽  
Jianming Wu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Type 2 Diabetes ◽  
Inhibitory Activity ◽  
Black Tea ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Inhibitory Peptides ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP-IV) inhibitors occupy a growing place in the drugs used for the management of type 2 diabetes. Recently, food components, including food-derived bioactive peptides, have been suggested as sources of DPP-IV inhibitors without side effects. Chinese black tea is a traditional health beverage, and it was used for finding DPP-IV inhibitory peptides in this study. The ultra-filtrated fractions isolated from the aqueous extracts of black tea revealed DPP-IV inhibitory activity in vitro. Four peptides under 1 kDa were identified by SDS-PAGE and LC-MS/MS (Liquid Chromatography-Mass Spectrometry-Mass Spectrometry) from the ultra-filtrate. The peptide II (sequence: AGFAGDDAPR), with a molecular mass of 976 Da, showed the greatest DPP-IV inhibitory activity (in vitro) among the four peptides. After administration of peptide II (400 mg/day) for 57 days to streptozotocin (STZ)-induced hyperglycemic mice, the concentration of glucagon-like peptide-1 (GLP-1) in the blood increased from 9.85 ± 1.96 pmol/L to 19.22 ± 6.79 pmol/L, and the insulin level was increased 4.3-fold compared to that in STZ control mice. Immunohistochemistry revealed the improved function of pancreatic beta-cells and suppressed proliferation of pancreatic alpha-cells. This study provides new insight into the use of black tea as a potential resource of food-derived DPP-IV inhibitory peptides for the management of type 2 diabetes.

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