A Dipeptide Module Substitution-Based Strategy for the Modification and Evaluation of ACE Inhibitory Peptides.
- 1College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.
- 2School of Ocean Food and Biological Engineering, Jiangsu Ocean University, Lianyungang 222005, China.
- 3Jiangsu Key Laboratory of Marine Bioresources and Environment/Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University, Lianyungang 222005, China.
Abstract
Food-derived angiotensin-converting enzyme (ACE) inhibitory peptide LYPVK exhibits promising potential for application as an important ingredient with a potential antihypertensive effect in functional foods. However, the structure-activity relationship and the rational design strategy for peptide modification remain insufficiently understood. To address this, dipeptide module substitution was employed to modify and investigate the mechanism of this food-derived ACE inhibitory peptide, providing an insight into the structure-activity relationship. Through integration of molecular docking and activity verification, LY and YP within LYPVK were identified as potential low- and high-activity fragments, respectively. Meanwhile, EY and SY were screened as high-contribution ones, resulting in the generation of EYPVK and SYPVK, which exhibited 13.5% and 25.1% higher ACE inhibitory activity, respectively, compared with the original peptide LYPVK. The enhanced activity may be attributed to increased hydrogen bonds and hydrophobic interactions with ACE and the strengthening of Tyr-mediated binding by Glu or Ser residues in the peptide sequences. Cellular assays showed altered nitric oxide (NO) and endothelin-1 (ET-1) levels, suggesting their potential function at the endothelial cell level. Additionally, SYPVK may regulate multiple targets and pathways for its function, as indicated by the network pharmacology and real-time fluorescence quantitative PCR analysis. These findings demonstrate that dipeptide module substitution is a viable approach for peptide optimization, highlighting the potential module effects in the design of functional peptides.
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BibTeX
@article{liang2026dipeptide,
title = {{A Dipeptide Module Substitution-Based Strategy for the Modification and Evaluation of ACE Inhibitory Peptides.}},
author = {Qingping Liang and Shuangtong Wang and Nana Sun and Changliang Zhu and Zhemin Liu and Haijin Mou},
journal = {Foods (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/foods15203617},
url = {https://europepmc.org/article/MED/42940256},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Dipeptide Module Substitution-Based Strategy for the Modification and Evaluation of ACE Inhibitory Peptides.
AU - Qingping Liang
AU - Shuangtong Wang
AU - Nana Sun
AU - Changliang Zhu
AU - Zhemin Liu
AU - Haijin Mou
PY - 2026
DA - 2026/10/11
JO - Foods (Basel, Switzerland)
DO - 10.3390/foods15203617
UR - https://europepmc.org/article/MED/42940256
AB - Food-derived angiotensin-converting enzyme (ACE) inhibitory peptide LYPVK exhibits promising potential for application as an important ingredient with a potential antihypertensive effect in functional foods. However, the structure-activity relationship and the rational design strategy for peptide modification remain insufficiently understood. To address this, dipeptide module substitution was employed to modify and investigate the mechanism of this food-derived ACE inhibitory peptide, providing an insight into the structure-activity relationship. Through integration of molecular docking and activity verification, LY and YP within LYPVK were identified as potential low- and high-activity fragments, respectively. Meanwhile, EY and SY were screened as high-contribution ones, resulting in the generation of EYPVK and SYPVK, which exhibited 13.5% and 25.1% higher ACE inhibitory activity, respectively, compared with the original peptide LYPVK. The enhanced activity may be attributed to increased hydrogen bonds and hydrophobic interactions with ACE and the strengthening of Tyr-mediated binding by Glu or Ser residues in the peptide sequences. Cellular assays showed altered nitric oxide (NO) and endothelin-1 (ET-1) levels, suggesting their potential function at the endothelial cell level. Additionally, SYPVK may regulate multiple targets and pathways for its function, as indicated by the network pharmacology and real-time fluorescence quantitative PCR analysis. These findings demonstrate that dipeptide module substitution is a viable approach for peptide optimization, highlighting the potential module effects in the design of functional peptides.
SN - 2304-8158
ER -