Bioactive peptides have been considered effective alternatives for the treatment of type 2 diabetes targeting the dipeptidyl peptidase-Ⅳ(DPP-Ⅳ).In this study,novel DPP-Ⅳinhibitory peptides were prepared and identif...Bioactive peptides have been considered effective alternatives for the treatment of type 2 diabetes targeting the dipeptidyl peptidase-Ⅳ(DPP-Ⅳ).In this study,novel DPP-Ⅳinhibitory peptides were prepared and identified from Musculus senhousei through two-stage chromatographic purification,peptidomic analysis,in silico screening,and validation.Furthermore,molecular simulation was employed to analyze the interaction from a molecular perspective.Results showed that Musculus senhousei hydrolysate produced by 8 h Neutrase hydrolysis exhibited the significant DPP-Ⅳinhibitory activity.Purification and identification led to the discovery of 387 peptide sequences.A total of 11 novel peptides with potential DPP-Ⅳinhibitory activity were screened in silico.Further synthesis and validation of peptide activity showed that LTWR and DPF significantly inhibit DPP-Ⅳin a competitive inhibitory manner,with IC_(50)values of 1788.67±28.13 and 1399.73±27.15μM,respectively.Results from molecular docking and dynamic simulations indicated that peptides LTWR and DPF could tightly bind to the catalytic site of DPP-Ⅳthrough hydrogen-bond and hydrophobic interaction.These findings suggested that Musculus senhousei could serve as a natural source of bioactive peptides for potential treatment of type 2 diabetes.展开更多
基金supported by the Key-Area Research and Development Program of Guangdong Province(2021B0707060001 and 2022B0202030001)the National Natural Science Foundation of China(No.32101896)+1 种基金the Self-innovation Research Funding Project of Hanjiang Laboratory(HJL202101B001)The Accreditation as Center of Excellence Severo Ochoa CEX2021-001189-S by MCIN/AEI/10.13039/501100011033 is also acknowledged.
文摘Bioactive peptides have been considered effective alternatives for the treatment of type 2 diabetes targeting the dipeptidyl peptidase-Ⅳ(DPP-Ⅳ).In this study,novel DPP-Ⅳinhibitory peptides were prepared and identified from Musculus senhousei through two-stage chromatographic purification,peptidomic analysis,in silico screening,and validation.Furthermore,molecular simulation was employed to analyze the interaction from a molecular perspective.Results showed that Musculus senhousei hydrolysate produced by 8 h Neutrase hydrolysis exhibited the significant DPP-Ⅳinhibitory activity.Purification and identification led to the discovery of 387 peptide sequences.A total of 11 novel peptides with potential DPP-Ⅳinhibitory activity were screened in silico.Further synthesis and validation of peptide activity showed that LTWR and DPF significantly inhibit DPP-Ⅳin a competitive inhibitory manner,with IC_(50)values of 1788.67±28.13 and 1399.73±27.15μM,respectively.Results from molecular docking and dynamic simulations indicated that peptides LTWR and DPF could tightly bind to the catalytic site of DPP-Ⅳthrough hydrogen-bond and hydrophobic interaction.These findings suggested that Musculus senhousei could serve as a natural source of bioactive peptides for potential treatment of type 2 diabetes.
