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In silico identification of novel ACE and DPP-IV inhibitory peptides derived from buffalo milk proteins and evaluation of their inhibitory mechanisms

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Abstract

The capacity of buffalo milk proteins to release bioactive peptides was evaluated and novel bioactive peptides were identified. The sequential similarity between buffalo milk proteins and their cow counterparts was analysed. Buffalo milk proteins were simulated to yield theoretical peptides via in silico proteolysis. The potential of selected proteins to release specific bioactive peptides was evaluated by the A value obtained from the BIOPEP–UWM database (Minkiewicz et al. in Int J Mol Sci 20(23):5978, 2019). Buffalo milk protein is a suitable precursor to produce bioactive peptides, particularly dipeptidyl peptidase IV (DPP-IV) and angiotensin I-converting enzyme (ACE) inhibitory peptides. Two novel ACE inhibitory peptides (KPW and RGP) and four potential DPP-IV inhibitory peptides (RGP, KPW, FPK and KFTW) derived from in silico proteolysis of buffalo milk proteins were screened using different integrated bioinformatic approaches (PeptideRanker, Innovagen, peptide-cutter and molecular docking). The Lineweaver–Burk plots showed that KPW (IC50 = 136.28 ± 10.77 μM) and RGP (104.72 ± 8.37 μM) acted as a competitive inhibitor against ACE. Similarly, KFTW (IC50 = 873.92 ± 32.89 μM) was also a competitive inhibitor of DPP-IV, while KPW and FPK (82.52 ± 10.37 and 126.57 ± 8.45 μM, respectively) were mixed-type inhibitors. It should be emphasized that this study does not involve any clinical trial.

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Acknowledgements

Authors are grateful to Xiuxiu Zhang for valuable discussion and assistance.

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  1. Yuxiang Gu and Xing Li have contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, Heilongjiang, China

    Yuxiang Gu, Xing Li, Xiaofen Qi & Ying Ma

  2. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore

    Eric Chun Yong Chan

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  1. Yuxiang Gu
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Contributions

Conceptualization, formal analysis, investigation and writing—original draft: YG. Conceptualization, formal analysis, investigation and writing—review and editing: XL. Writing—review and editing: XQ. Resources and supervision: YM. Writing—review and editing: ECYC.

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Correspondence to Ying Ma or Eric Chun Yong Chan.

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Gu, Y., Li, X., Qi, X. et al. In silico identification of novel ACE and DPP-IV inhibitory peptides derived from buffalo milk proteins and evaluation of their inhibitory mechanisms. Amino Acids 55, 161–171 (2023). https://doi.org/10.1007/s00726-022-03202-z

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