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Potential antidiabetic activity and permeability assessment of the modified yeast-derived peptide, VLSTSFPPW (VW9)

  • 1Department of Environmental Technology, Food Technology, and Molecular Biotechnology, Ghent University Global Campus, 21985, Incheon, South Korea.
  • 2Department of Biotechnology, Iranian Research Organization for Science & Technology (IROST), Tehran, Iran.
  • 3Department of Biology, California State University, Fresno, CA 93740, USA.
  • 4School of Life Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
  • 5Department of Agricultural, Food and Nutritional Science, 4-10 Ag/For Building, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.; Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta T6G 2R7, Canada.
  • 6Unit Food Chemistry and Human Nutrition (nutriFOODchem), Faculty of Bio-Science Engineering, Ghent University Coupure Links 653, B-9000 Ghent, Belgium. Electronic address: charlotte.grootaert@ugent.be.
  • 7Unit Food Chemistry and Human Nutrition (nutriFOODchem), Faculty of Bio-Science Engineering, Ghent University Coupure Links 653, B-9000 Ghent, Belgium. Electronic address: john.vancamp@ugent.be.
  • 8Department of Environmental Technology, Food Technology, and Molecular Biotechnology, Ghent University Global Campus, 21985, Incheon, South Korea.; Unit Food Chemistry and Human Nutrition (nutriFOODchem), Faculty of Bio-Science Engineering, Ghent University Coupure Links 653, B-9000 Ghent, Belgium. Electronic address: mahta.mirzaei@ghent.ac.kr.
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June 14, 2025

Abstract

This study investigates the antidiabetic activity, gastrointestinal stability, and permeability of a modified yeast-derived peptide, VLSTSFPPW (VW9), using in vitro gastrointestinal digestion and Caco-2 cell models. LC-MS/MS analysis revealed that VW9 with DPP-IV inhibitory activity, was extensively cleaved during digestion into smaller fragments like PPW, FPPW, FPP, ST, and SFPP. Among these, PPW displayed the highest activity in vitro (IC50: 22.60 ± 0.18 μM) and in situ (IC50: 474 ± 10.2 μM). Kinetic and molecular docking studies indicated that PPW may inhibit the DPP-IV enzyme in a competitive way mainly due to hydrogen-bond interactions between Trp residue at C-terminus of PPW and the active site residues of DPP-IV. PPW could not penetrate epithelial cells, but a modified derivative was found on both apical and basolateral sides without DPP-IV inhibitory activity. These findings highlight the challenges of stability, activity, and permeability of VW9 and its derived peptides for potential therapeutic applications.

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