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

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 ala...

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Bibliographic Details
Published in:International journal of biological macromolecules 2020-10, Vol.160, p.1220-1229
Main Authors: Ibrahim, Mohammed Auwal, Serem, June C., Bester, Megan J., Gaspar, Anabella R.M.
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes - drug effects
Adipocytes - metabolism
Alanine - chemistry
Alanine - genetics
Alanine scanning
Amino Acid Substitution
Animals
Binding Sites
Dipeptidyl Peptidase 4 - chemistry
Dipeptidyl Peptidase 4 - metabolism
Dipeptidyl-Peptidase IV Inhibitors - chemistry
Dipeptidyl-Peptidase IV Inhibitors - metabolism
Free Radical Scavengers - chemistry
Free Radical Scavengers - pharmacology
Humans
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - metabolism
Lipid Metabolism
Mice
Molecular Docking Simulation
Oligopeptides - chemistry
Oligopeptides - genetics
Oligopeptides - metabolism
Oxidative Stress
Protein Binding
SQSPA
Structure-Activity Relationship
Type 2 diabetes
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Summary: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 
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2020.05.250