Rational module substitution strategy to enhance ACE-inhibitory peptide activity
Qingping Liang1, Siyuan Peng1, Zhemin Liu1
1College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.
Food Chemistry
|September 4, 2025
Summary
Module substitution enhances food-derived peptide activity for hypertension prevention. Replacing specific peptide modules improved angiotensin-converting enzyme (ACE) inhibition and antihypertensive effects.
Area of Science:
- Biochemistry
- Molecular Biology
- Nutritional Science
Background:
- Food-derived peptides show potential for hypertension prevention by inhibiting angiotensin-converting enzyme (ACE).
- Peptide activity is significantly influenced by specific amino acid sequences and module composition.
- Optimizing these sequences is crucial for developing effective antihypertensive agents.
Purpose of the Study:
- To enhance the activity of food-derived ACE-inhibitory peptides through a strategic module substitution approach.
- To identify high-contribution dipeptide modules within ACE-inhibitory peptides.
- To investigate the impact of substituting low-contribution modules on overall peptide efficacy.
Main Methods:
- Utilized molecular docking and in vitro activity assays to evaluate dipeptide module contributions.
- Systematically screened alternative dipeptide modules for substitution into the parent peptide sequence.
- Assessed the ACE-inhibitory and antihypertensive effects of modified peptide sequences using cellular assays.
Main Results:
- Identified MF as a low-contribution and FP as a high-contribution module in the MFPWP peptide.
- CF, TF, VF, and PF emerged as high-contribution alternative modules for substitution.
- Novel peptides (CFPWP, TFPWP, VFPWP, PFPWP) exhibited 21.30%-67.07% greater ACE inhibition than MFPWP.
- Enhanced peptides demonstrated improved antihypertensive effects, including increased nitric oxide (NO) release and reduced endothelin-1 (ET-1) levels.
Conclusions:
- Module substitution is a viable strategy for enhancing the bioactivity of food-derived peptides.
- Specific dipeptide modules significantly impact ACE inhibition and antihypertensive properties.
- This study provides a framework for designing improved bioactive peptides through targeted sequence modification.
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