Combinatorial peptide library screening for discovery of diverse α-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models

Mollica, Adriano; Zengin, Gökhan; Durdağı, Serdar; Salmas, Ramin Ekhteiari; Macedonio, Giorgia; Stefanucci, Azzurra; Dimmito, Marilisa Pia; Novellino, Ettore

doi:10.1080/07391102.2018.1439403

Cited by 76 publications

(41 citation statements)

References 28 publications

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“…The results in Table show that the largest dipole moment occurs at 373 K with a SEF of 1 V/nm. However, studies have reported that alpha‐amylase and trypsin inhibitors are considered as potential antiobesity molecules . Thus, the functional properties of RATI after related processing methods, especially high temperature treatments, are needed to be evaluated in the future.…”

Section: Resultsmentioning

confidence: 99%

Computational evaluation of the effect of processing on the trypsin and alpha‐amylase inhibitor from Ragi (Eleusine coracana) seed

Fenwick

Vanga

DiNardo

et al. 2019

Engineering Reports

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Ragi, also known as Finger millet, has been promoted as a healthy alternative to major cereals such as rice and wheat. It is a well‐known source of various minerals, dietary fiber, and a primary source of carbohydrate in parts of Asia and Africa. Ragi is a drought resistant crop, hence, useful for adapting to the current climate change and depleting water resource conditions in various parts of the world. However, the Ragi is known to have poor digestibility, primarily due to the presence of antinutritional compounds like alpha‐amylase and trypsin inhibitor. We have studied temperature, static electric fields (SEFs) and oscillating electric fields (OEFs) to evaluate the secondary structure changes of alpha‐amylase and trypsin inhibitor molecule in Ragi. This was simulated at three temperatures: 300, 343, and 373 K with SEF and OEF at an intensity of 1 V/nm with a frequency of 2.45 GHz (for OEF). STRIDE analysis exhibits various changes in the secondary structure of the protein, especially the loop connecting the alpha helices together. Thermal processing alone has also affected the second alpha helix of the molecule. Overall, the SEFs of 1 V/nm are found to have resulted in the most secondary structure deviations in terms of root mean square deviation and radius of gyration.

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Section: Resultsmentioning

confidence: 99%

Computational evaluation of the effect of processing on the trypsin and alpha‐amylase inhibitor from Ragi (Eleusine coracana) seed

Fenwick

Vanga

DiNardo

et al. 2019

Engineering Reports

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“…There are studies about peptide inhibitory α-glucosidase where carried out with molecular docking models. According to the Mollica et al [31], the crystallographic ligand acarbose interacts with α-glucosidase in the enzymatic cavity by establishing several hydrogen-bond (H-bond) interactions. In particular, the key interactions involve Asp1157, Asp1279, Lys1460, Arg1510, Asp1526, His1584.…”

Section: Evaluation Of the Activity Of Hydrolysates After The Simulatmentioning

confidence: 99%

Evaluation of ACE, α-glucosidase, and lipase inhibitory activities of peptides obtained by in vitro digestion of selected species of edible insects

Zielińska

Karaś

Baraniak

et al. 2020

Eur Food Res Technol

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The objective of this study was to examine the inhibition of the activity of enzymes associated with development of the metabolic syndrome by peptide fractions received from simulated gastrointestinal digestion and absorption of heat-treated edible insects. The inhibitory activities of insect-derived peptides were determined against key enzymes relevant to the metabolic syndrome such as the angiotensin-converting enzyme (ACE), pancreatic lipase, and α-glucosidase. After the in vitro absorption process, all hydrolysates showed high inhibitory activity; however, the most effective metabolic syndrome-inhibitory peptides were received after separation on Sephadex G10. The best results were found for peptide fractions obtained from Schistocerca gregaria. The highest enzymes inhibitory activities were obtained for peptide fractions from S. gregaria: boiled for ACE (IC 50 3.95 µg mL −1), baked for lipase (IC 50 9.84 µg mL −1), and raw for α-glucosiadase (IC 50 1.89 µg mL −1) S. gregaria, respectively. Twelve sequences of peptides from the edible insects were identified and their chemical synthesis was carried out as well. Among the synthesized peptides, the KVEGDLK, YETGNGIK, AIGVGAIR, IIAPPER, and FDPFPK sequences of peptides exhibited the highest inhibitory activity. Generally, the heat treatment process applied to edible insects has a positive effect on the properties of the peptide fractions studied.

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“…Mouse vas deferens (NMRI mice, 35-45 g) was prepared as described before [26]. After the preparation vas deferens were suspended in 5 ml organ baths containing Mg 2+ free Krebs buffer (118.1 mM NaCl, 25 mM NaHCO3, 4.7 mM KCl, 11 mM glucose, 1.2 mM KH2PO4, 1.8 mM CaCl2) and aerated with carbogen (O2:CO2=95:5) at 31 C.…”

Section: Mouse Vas Deferens Bioassaymentioning

confidence: 99%

Biochemical and pharmacological investigation of novel nociceptin/OFQ analogues and N/OFQ-RYYRIK hybrid peptides

et al. 2019

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The endogenous ligand nociceptin (N/OFQ) and a positively charged synthetic peptide RYYRIK are both selective for the nociceptin opioid receptor (NOPr). Despite their structural dissimilarity, N/OFQ and RYYRIK compete for the same binding site of NOP receptor possessing full and partial agonistic character, respectively. In the view of the messageaddress concept, hybrid peptide constructs were probed for the NOP receptor combining different regions of N/OFQ and RYYRIK related peptide sequences. Nine novel nociceptinor Ac-RYYRIK-NH2 peptide variants or hybrid peptides were synthesized and characterized. Peptides P2 and P8 contain fragments of native N/OFQ. The other seven analogues (P1, P3-7, P9) are composed of Ac-RYYRIK-NH2 fragments and parts of the original nociceptin sequence. The analogues were characterized in receptor binding assays and G-protein activation experiments on rat brain membranes, as well as by electrically stimulated mouse vas deferens bioassay. In receptor binding assays ligands P2 , P4 , P6 (Ki 0.37 nM) and P7 showed higher affinity (Ki 0.65 nM, 0.6 nM, 0.37 nM and 0.44 nM, respectively) for NOP receptor than their parent compounds N/OFQ (Ki 2.8 nM) or Ac-RYYRIK-NH2 (Ki 4.2 nM). In [ 35 S]GTPγS binding experiments P2 and P3 behaved as full agonists. The other variants exhibited partial agonist properties characterized by submaximal stimulatory effects. In mouse vas deferens bioassay only P2 showed agonist activity. P4, P5, P6 inhibited the biological activity of N/OFQ more effectively than the NOP receptor selective antagonist JTC-801. In summary, hybrid peptides P4, P5 and P6 proved to be NOP receptor partial agonists even antagonists, while P2 peptide retained the full agonist property.

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Combinatorial peptide library screening for discovery of diverse α-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models

Cited by 76 publications

References 28 publications

Computational evaluation of the effect of processing on the trypsin and alpha‐amylase inhibitor from Ragi (Eleusine coracana) seed

Computational evaluation of the effect of processing on the trypsin and alpha‐amylase inhibitor from Ragi (Eleusine coracana) seed

Evaluation of ACE, α-glucosidase, and lipase inhibitory activities of peptides obtained by in vitro digestion of selected species of edible insects

Biochemical and pharmacological investigation of novel nociceptin/OFQ analogues and N/OFQ-RYYRIK hybrid peptides

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