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dc.contributor.author | Ibrahim, Mohammed Auwal![]() |
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dc.contributor.author | Bester, Megan Jean![]() |
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dc.contributor.author | Neitz, Albert Walter Herman![]() |
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dc.contributor.author | Gaspar, Anabella Regina Marques![]() |
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dc.date.accessioned | 2018-10-23T05:26:31Z | |
dc.date.issued | 2018-11 | |
dc.description.abstract | Treatment of type 2 diabetes is achieved through the inhibition of carbohydrate hydrolyzing enzymes such as α-glucosidase and α-amylase. The present study was conducted to identify novel α-glucosidase inhibitory peptides and to validate the α-glucosidase and α-amylase inhibitory activities of two promising candidates. A total of 4210 potential α-glucosidase inhibitory peptides with 3–5 amino acid residues were designed and individually subjected to in silico simulated gastrointestinal (GIT) digestion using the BIOPEP database. Subsequently, 844 GIT resistant peptides were then subjected to molecular docking using Autodock Vina to determine their binding free energy against human α-glucosidase (PDB ID: 3L4Y). Among all the peptides, SVPA and SEPA were found to have the lowest binding free energies of -8.7 and -8.6 kcal/mol, respectively. Docking of SVPA and SEPA on human α-amylase (PDB ID, 4GQR) identified that both peptides also bind to α-amylase with binding energies of -6.5 and -6.9 kcal/mol, respectively. Hydrogen bond interactions were critical for the binding of both peptides to the α-glucosidase and α-amylase. In vitro, SVPA and SEPA inhibited α-glucosidase and α-amylase activities with IC50 values several fold lower than acarbose except for SVPA that had a significantly higher (p < 0.05) IC50 value than acarbose against α-glucosidase. Lineweaver-Burk analyses revealed that SVPA was an uncompetitive inhibitor of the two enzymes, while SEPA inhibited α-glucosidase and α-amylase non-competitively and uncompetitively, respectively. This study has identified two novel and active α-glucosidase inhibitory peptides that could resist GIT digestion and therefore, have the potential to retard postprandial hyperglycemia in diabetic patients. | en_ZA |
dc.description.department | Anatomy | en_ZA |
dc.description.department | Biochemistry | en_ZA |
dc.description.embargo | 2019-11-01 | |
dc.description.librarian | hj2018 | en_ZA |
dc.description.sponsorship | The National Research Foundation of South Africa and the University of Pretoria. The first author also acknowledges the University of Pretoria for the award of a postdoctoral fellowship position in Biochemistry and Ahmadu Bello University, Zaria, Nigeria for the award of a study fellowship. | en_ZA |
dc.description.uri | http://www.elsevier.com/locate/biopha | en_ZA |
dc.identifier.citation | Ibrahim, M.A., Bester, M.J., Neitz, A.W. & Gaspar, A.R.M. 2018, 'Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates', Biomedicine and Pharmacotherapy, vol. 107, pp. 234-242. | en_ZA |
dc.identifier.issn | 0753-3322 (print) | |
dc.identifier.issn | 1950-6007 (online) | |
dc.identifier.other | 10.1016/j.biopha.2018.07.163 | |
dc.identifier.uri | http://hdl.handle.net/2263/67018 | |
dc.language.iso | en | en_ZA |
dc.publisher | Elsevier | en_ZA |
dc.rights | © 2018 Elsevier Masson SAS. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Biomedicine and Pharmacotherapy. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Biomedicine and Pharmacotherapy, vol. 107, pp. 234-242, 2018. doi : 10.1016/j.biopha.2018.07.163. | en_ZA |
dc.subject | Bioactive peptides | en_ZA |
dc.subject | Diabetes mellitus | en_ZA |
dc.subject | Alpha-Glucosidase inhibitors | en_ZA |
dc.subject | Gastrointestinal digestion | en_ZA |
dc.subject | In silico analysis | en_ZA |
dc.subject | Molecular docking | en_ZA |
dc.subject | Angiotensin converting enzyme (ACE) | en_ZA |
dc.subject | Pumpkin | en_ZA |
dc.subject | Proteins | en_ZA |
dc.subject | Amylase | en_ZA |
dc.subject | Management | en_ZA |
dc.subject.other | Health sciences article SDG-03 | |
dc.subject.other | SDG-03: Good health and well-being | |
dc.title | Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates | en_ZA |
dc.type | Postprint Article | en_ZA |