Long-acting peptidomimetics based DPP-IV inhibitors

Jadav, Pradip; Bahekar, Rajesh; Shah, Shailesh R.; Patel, Dipam; Joharapurkar, Amit; Kshirsagar, Samadhan; Jain, Mukul; Shaikh, Mubeen; Sairam, Kalapatapu V.V.M.

doi:10.1016/j.bmcl.2012.03.078

Cited by 24 publications

(29 citation statements)

References 26 publications

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“…It is interesting that most of the flavonoids tested in the present study showed lower IC 50 values and therefore were more potent than the reference inhibitor standard diprotin A. Resveratrol, luteolin, apigenin and flavone showed the most potent DPP-IV inhibitory activity due to their lowest IC 50 values. In particular, this study demonstrated that resveratrol was the most potent DPP-IV inhibitor with IC 50 value at 0.6 nM exhibiting even lower values than sitagliptin (18 nM) and vildagliptin (3.5 nM) [10], two current pharmacologic drug inhibitors of DPP-IV. A summary of current foods and food components in the prevention of diabetes by Thomas and Pfeiffer [16] has indicated that the potential evidence for phenolic compounds is not conclusive; however, resveratrol was found to have a beneficial effect on protecting beta cells, which may be due to its ability to modulate the activity of DPP-IV.…”

Section: Discussionmentioning

confidence: 99%

“…The specificity pocket S1 is composed of the side chains of catalytic triad (Ser630, Asn710, and His740), which are involved in strong hydrophobic interactions [10]. The cavity near Glu205, Glu206 and Tyr662 residues is referred to as the S2 pocket.…”

Section: Discussionmentioning

confidence: 99%

“…For DPP-IV, computational docking analyses have been commonly used for designing inhibitors [9], screening of potential inhibitors [10], and explaining the differences in activity of drugs with different structures [11]. However, most of the previously investigated inhibitors of DPP-IV have been synthetically derived.…”

Section: Introductionmentioning

confidence: 99%

“…Phenolic compounds, such as flavonoids, widely abundant in fruits and vegetables, have been suggested as important compounds for diabetes reduction [9, 10]. However, so far only a few phenolic compounds have been investigated to inhibit DPP-IV activity.…”

Section: Introductionmentioning

confidence: 99%

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Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

Fan

Johnson

Lila

et al. 2013

Evidence-Based Complementary and Alternative Medicine

141

148

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Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content. Dipeptidyl peptidase IV (DPP-IV) is a serine aminopeptidase that is a novel target for type 2 diabetes therapy due to its incretin hormone regulatory effects. In this study, well-characterized anthocyanins (ANC) isolated from berry wine blends and twenty-seven other phenolic compounds commonly present in citrus, berry, grape, and soybean, were individually investigated for their inhibitory effects on DPP-IV by using a luminescence assay and computational modeling. ANC from blueberry-blackberry wine blends strongly inhibited DPP-IV activity (IC50, 0.07 ± 0.02 to >300 μM). Of the twenty-seven phenolics tested, the most potent DPP-IV inhibitors were resveratrol (IC50, 0.6 ± 0.4 nM), luteolin (0.12 ± 0.01 μM), apigenin (0.14 ± 0.02 μM), and flavone (0.17 ± 0.01 μM), with IC50 values lower than diprotin A (4.21 ± 2.01 μM), a reference standard inhibitory compound. Analyses of computational modeling showed that resveratrol and flavone were competitive inhibitors which could dock directly into all three active sites of DPP-IV, while luteolin and apigenin docked in a noncompetitive manner. Hydrogen bonding was the main binding mode of all tested phenolic compounds with DPP-IV. These results indicate that flavonoids, particularly luteolin, apigenin, and flavone, and the stilbenoid resveratrol can act as naturally occurring DPP-IV inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

Fan

Johnson

Lila

et al. 2013

Evidence-Based Complementary and Alternative Medicine

141

148

View full text Add to dashboard Cite

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“…Fig. 5C shows the way the peptide interacted with the active site of DPP-IV (Jadav et al, 2012); the amino acids of the S1 pocket (SER630, ASN710, HIS740) labeled in orange, S2 pocket (GLU205, GLU206) in purple, and S3 pocket (SER209, PHE357, ARG358) in red. A red surface around the active site of DPP-IV (Fig.…”

Section: Computational Modeling For Interaction Of Dpp-iv and A Commomentioning

confidence: 98%

Germination of Phaseolus vulgaris and alcalase hydrolysis of its proteins produced bioactive peptides capable of improving markers related to type-2 diabetes in vitro

Rocha

Hernandez

Mojica

et al. 2015

Food Research International

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The aim of this study was to evaluate the effect of germination and alcalase hydrolysis of common bean proteins on the generation of bioactive peptides with potential to reduce parameters related to the risk of developing type-2 diabetes (T2D) in vitro. Germination (25°C up to 72 h) and alcalase hydrolysis (up to 4 h) produced peptides with high antioxidant capacity (1085 μmol TE/g soluble protein, SP). After 24 h of germination, there was an increase of 44% in α-amylase inhibitory capacity of the peptides relative to acarbose (1 mM). Simulated gastrointestinal digestion of the non-germinated and non-hydrolyzed sample (G0-0h) produced bioactive peptides that inhibited dipeptidyl peptidase-IV (DPP-IV) (IC 50 = 1.2 mg SP/mL); however, the IC 50 was not improved by either germination or alcalase hydrolysis. Insulin secretion by glucose stimulated (20 mM) INS-1E pancreatic β-cells, increased 45% from the basal state with 2 mg SP/mL of G0-0h. Germination did not improve the stimulation of insulin. Computational modeling showed that the peptide RGPLVNPDPKPFL obtained after 48 h germination and 1 h alcalasehydrolysis was able to inhibit DPP-IV by interacting with its S1, S2, and S3 pockets of the active site. Germination and alcalase hydrolysis can be applied to improve some markers related to the management of T2D. Furthermore, simulated gastrointestinal digestion of common bean proteins without any treatment produced bioactive peptides with the ability to inhibit DPP-IV, resulting in increased insulin released from pancreatic cells in vitro.

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Thermal Rearrangement of Azido Ketones into Oxazoles via Azirines: One‐Pot, Metal‐Free Heteroannulation to Functionalized 1,3‐Oxazoles

et al. 2012

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Long-acting peptidomimetics based DPP-IV inhibitors

Cited by 24 publications

References 26 publications

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

Germination of Phaseolus vulgaris and alcalase hydrolysis of its proteins produced bioactive peptides capable of improving markers related to type-2 diabetes in vitro

Thermal Rearrangement of Azido Ketones into Oxazoles via Azirines: One‐Pot, Metal‐Free Heteroannulation to Functionalized 1,3‐Oxazoles

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