The dipeptidyl peptidase IV inhibitory activity and multifunctional antidiabetic properties of SQSPA : structure – activity relationship evaluated with alanine scanning

dc.contributor.authorIbrahim, Mohammed Auwal
dc.contributor.authorSerem, June Cheptoo
dc.contributor.authorBester, Megan Jean
dc.contributor.authorGaspar, Anabella Regina Marques
dc.date.accessioned2020-12-31T07:32:35Z
dc.date.issued2020-10
dc.description.abstractType 2 diabetes is a multifactorial disease and drugs with multifunctional properties are required. The peptide, SQSPA, was reported to be a potent and gastrointestinally stable α-glucosidase inhibitory peptide. In this study, the structure-activity relationship of this peptide was studied using alanine scanning. Four analogs; AQSPA, SASPA, SQAPA and SQSAA were designed and investigated for multifunctional antidiabetic effects. Molecular docking studies on human dipeptidyl peptidase-IV (DPP-IV) suggested that the binding affinities were in the order; AQSPA>SASPA>SQSPA>SQSAA>SQAPA while for in vitro DPP-IV inhibitory activity, it was SQSPA>SQSAA>AQSPA>SASPA>SQAPA. Enzyme kinetic studies revealed that the peptides are uncompetitive inhibitors with the exception of SQSAA and SQSPA. In 3T3-L1 differentiated adipocytes, SASPA was the only analog that significantly (p < 0.05) reduced and prevented lipid accumulation and did not induce cytotoxicity to differentiated 3T3-L1 cells. All peptides, especially SASPA scavenged methylglyoxal and peroxyl radicals thereby preventing advanced glycosylated end products formation and oxidative stress. The nitric oxide scavenging activity of all peptides was comparable to IPI and glutathione. Findings indicate that the amide side chain of Q2 is probably the most critical functional group for modulating the multifunctional antidiabetic effects of SQSPA while SASPA has been identified, as a novel peptide with enhanced multifunctional antidiabetic activity.en_ZA
dc.description.departmentAnatomyen_ZA
dc.description.departmentBiochemistryen_ZA
dc.description.departmentGeneticsen_ZA
dc.description.departmentMicrobiology and Plant Pathologyen_ZA
dc.description.embargo2021-10-01
dc.description.librarianhj2020en_ZA
dc.description.sponsorshipThe National Research Foundation of South Africa and the University of Pretoria.en_ZA
dc.description.urihttp://www.elsevier.com/locate/ijbiomacen_ZA
dc.identifier.citationIbrahim, M.A., Serem, J.C., Bester, M.J. et al. 2020, 'The dipeptidyl peptidase IV inhibitory activity and multifunctional antidiabetic properties of SQSPA : structure – activity relationship evaluated with alanine scanning', International Journal of Biological Macromolecules, vol. 160, pp. 1220-1229.en_ZA
dc.identifier.issn0141-8130
dc.identifier.other10.1016/j.ijbiomac.2020.05.250
dc.identifier.urihttp://hdl.handle.net/2263/77908
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2020 Elsevier B.V. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in International Journal of Biological Macromolecules. 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 International Journal of Biological Macromolecules, vol. 160, pp. 1220-1229, 2020. doi : 10.1016/j.ijbiomac.2020.05.250.en_ZA
dc.subjectAlanine scanningen_ZA
dc.subjectSQSPAen_ZA
dc.subjectType 2 diabetes mellitus (T2DM)en_ZA
dc.subject.otherHealth sciences articles SDG-03
dc.subject.otherSDG-03: Good health and well-being
dc.titleThe dipeptidyl peptidase IV inhibitory activity and multifunctional antidiabetic properties of SQSPA : structure – activity relationship evaluated with alanine scanningen_ZA
dc.typePostprint Articleen_ZA

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