Abstract
Various peptides with inhibitory activity against human dipeptidyl peptidase-IV (hDPP-IV), which degrades glucagon-like peptide 1 (GLP-1) and decreases insulin release, were isolated from synthetic tripeptide mixtures, having sequences Val-Pro-Xaa (VPX) or Ile-Pro-Xaa (IPX). All peptides isolated by reversed-phase high performance liquid chromatography (HPLC) analysis were measured for hDPP-IV inhibitory activity. VPV and VPI prepared from the VPX mixture and IPI isolated from the IPX mixture, showed the highest hDPP-IV inhibitory activity. The dissociation constants for hDPP-IV and IC50 values of the peptides were analyzed to understand the reason for the potent inhibitory activity of these tripeptides. The IC50 and Ki values of VPV, VPI, and IPI were found to be 20.2, 22.2, and 46.7 µM and 10.8, 11.3 and 21.4 M−1, respectively. Further, degradation of the peptides by the proteolytic action of hDPP-IV was analyzed to understand the stability of these peptides. Peptides with lower Ki and IC50 values showed relatively slower degradation when incubated with hDPP-IV. These results suggested that a peptide might have higher hDPP-IV inhibitory activity because of its higher affinity and stronger resistance to hDPP-IV, which is caused by the introduction of a hydrophobic amino acid at the C-terminal end of its VP or IP sequence.
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Acknowledgements
Changge Guan gratefully acknowledges the financial support provided by the China Scholarship Council (No. 201806210223), who supported his study in Tokyo Institute of Technology.
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Guan, C., Iwatani, S., Xing, Xh. et al. Strategic Preparations of DPP-IV Inhibitory Peptides from Val-Pro-Xaa and Ile-Pro-Xaa Peptide Mixtures. Int J Pept Res Ther 27, 735–743 (2021). https://doi.org/10.1007/s10989-020-10122-7
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DOI: https://doi.org/10.1007/s10989-020-10122-7