Structure – function analysis of peptide analogs of SQSPA with respect to α-glucosidase and α-amylase inhibition

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dc.contributor.author Ibrahim, Mohammed Auwal
dc.contributor.author Serem, June Cheptoo
dc.contributor.author Bester, Megan Jean
dc.contributor.author Neitz, Albert Walter Herman
dc.contributor.author Gaspar, Anabella Regina Marques
dc.date.accessioned 2020-08-21T09:07:41Z
dc.date.available 2020-08-21T09:07:41Z
dc.date.issued 2019-07
dc.description.abstract BACKGROUND : Peptide-based therapeutics offer a unique avenue for the development of novel agents for the treatment of diabetes mellitus including α-glucosidase inhibitors. The peptide, SQSPA, was reported to possess to α -glucosidase inhibitory activity in addition to resistance to Gastrointestinal Tract (GIT) digestion. METHODS : In this study, the in silico and in vitro structure-activity analyses of the peptide was conducted using alanine scanning to identify key amino acid residues. RESULTS : The alanine scanning led to four analogs viz; AQSPA, SASPA, SQAPA and SQSAA which were GIT stable. Initially, the peptides were subjected to molecular docking on human α- glucosidase and α -amylase where the binding affinities to the enzymes were in the order; AQSPA>SASPA>SQSPA>SQAPA> SQSAA and AQSPA>SQSAA>SASPA>SQSPA> SQAPA, respectively. Hydrogen bond were important for the binding of all peptides but SASPA and AQSPA had the highest hydrogen bonds interactions with the α-glucosidase and α-amylase, respectively. In vitro analysis revealed that the α -glucosidase and α-amylase inhibitory activities of the peptides were in the order AQSPA>SQSPA>SQAPA>SASPA>SQSAA and AQSPA>SASPA> SQAPA>SQSPA>SQSAA, respectively. Using inhibition kinetics, SQSPA was a mixed inhibitor of α-glucosidase while AQSPA, SQAPA and SQSAA showed non-competitive inhibition. For α- amylase inhibition, SQSPA was a non-competitive inhibitor while AQSPA and SQSAA were mixed inhibitors; SASPA and SQAPA showed uncompetitive inhibition. CONCLUSION : The results indicated that P4 and Q2 are important requirements for the α-glucosidase and α-amylase inhibitory activities of the parent peptide, SQSPA. Furthermore, alanine scanning has led to the design of a novel α-glucosidase inhibitory peptide, AQSPA, with increased activities. 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.librarian hj2020 en_ZA
dc.description.sponsorship The National Research Foundation of South Africa and the University of Pretoria. en_ZA
dc.description.uri https://benthamscience.com/journals/protein-and-peptide-letters en_ZA
dc.identifier.citation Ibrahim, M.A., Serem, J.C., Bester, M.J., Neitz, A.W., Gaspar, A.R.M. Structure - Function Analysis of Peptide Analogs of SQSPA with Respect to α-glucosidase and α-amylase Inhibition. Protein and Peptide Letters 2019;26(6):403-413. doi:10.2174/0929866526666190327121731. en_ZA
dc.identifier.issn 0929-8665 (print)
dc.identifier.issn 1875-5305 (online)
dc.identifier.other 10.2174/0929866526666190327121731
dc.identifier.uri http://hdl.handle.net/2263/75840
dc.language.iso en en_ZA
dc.publisher Bentham Science en_ZA
dc.rights © 2019 Bentham Science Publishers en_ZA
dc.subject Gastrointestinal tract (GIT) en_ZA
dc.subject Alanine scanning en_ZA
dc.subject Diabetes mellitus en_ZA
dc.subject Disaccharidase en_ZA
dc.subject Peptide-based therapeutics en_ZA
dc.subject Structure-activity relationship en_ZA
dc.subject Amino acid residues en_ZA
dc.subject.other Health sciences articles SDG-03
dc.subject.other SDG-03: Good health and well-being
dc.title Structure – function analysis of peptide analogs of SQSPA with respect to α-glucosidase and α-amylase inhibition en_ZA
dc.type Postprint Article en_ZA


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