Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates

dc.contributor.authorIbrahim, Mohammed Auwal
dc.contributor.authorBester, Megan Jean
dc.contributor.authorNeitz, Albert Walter Herman
dc.contributor.authorGaspar, Anabella Regina Marques
dc.date.accessioned2018-10-23T05:26:31Z
dc.date.issued2018-11
dc.description.abstractTreatment 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.departmentAnatomyen_ZA
dc.description.departmentBiochemistryen_ZA
dc.description.embargo2019-11-01
dc.description.librarianhj2018en_ZA
dc.description.sponsorshipThe 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.urihttp://www.elsevier.com/locate/biophaen_ZA
dc.identifier.citationIbrahim, 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.issn0753-3322 (print)
dc.identifier.issn1950-6007 (online)
dc.identifier.other10.1016/j.biopha.2018.07.163
dc.identifier.urihttp://hdl.handle.net/2263/67018
dc.language.isoenen_ZA
dc.publisherElsevieren_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.subjectBioactive peptidesen_ZA
dc.subjectDiabetes mellitusen_ZA
dc.subjectAlpha-Glucosidase inhibitorsen_ZA
dc.subjectGastrointestinal digestionen_ZA
dc.subjectIn silico analysisen_ZA
dc.subjectMolecular dockingen_ZA
dc.subjectAngiotensin converting enzyme (ACE)en_ZA
dc.subjectPumpkinen_ZA
dc.subjectProteinsen_ZA
dc.subjectAmylaseen_ZA
dc.subjectManagementen_ZA
dc.subject.otherHealth sciences articles SDG-03
dc.subject.otherSDG-03: Good health and well-being
dc.titleRational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidatesen_ZA
dc.typePostprint Articleen_ZA

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