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dc.contributor.author | Ibrahim, Mohammed Auwal![]() |
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dc.contributor.author | Serem, June Cheptoo![]() |
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dc.contributor.author | Bester, Megan Jean![]() |
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dc.contributor.author | Gaspar, Anabella Regina Marques![]() |
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dc.date.accessioned | 2020-12-31T07:32:35Z | |
dc.date.issued | 2020-10 | |
dc.description.abstract | Type 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.department | Anatomy | en_ZA |
dc.description.department | Biochemistry | en_ZA |
dc.description.department | Genetics | en_ZA |
dc.description.department | Microbiology and Plant Pathology | en_ZA |
dc.description.embargo | 2021-10-01 | |
dc.description.librarian | hj2020 | en_ZA |
dc.description.sponsorship | The National Research Foundation of South Africa and the University of Pretoria. | en_ZA |
dc.description.uri | http://www.elsevier.com/locate/ijbiomac | en_ZA |
dc.identifier.citation | Ibrahim, 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.issn | 0141-8130 | |
dc.identifier.other | 10.1016/j.ijbiomac.2020.05.250 | |
dc.identifier.uri | http://hdl.handle.net/2263/77908 | |
dc.language.iso | en | en_ZA |
dc.publisher | Elsevier | en_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.subject | Alanine scanning | en_ZA |
dc.subject | SQSPA | en_ZA |
dc.subject | Type 2 diabetes mellitus (T2DM) | en_ZA |
dc.subject.other | Health sciences article SDG-03 | |
dc.subject.other | SDG-03: Good health and well-being | |
dc.title | The dipeptidyl peptidase IV inhibitory activity and multifunctional antidiabetic properties of SQSPA : structure – activity relationship evaluated with alanine scanning | en_ZA |
dc.type | Postprint Article | en_ZA |