Identification and action mechanism of low-molecular-weight peptides derived from Atlantic salmon (Salmo salar L.) skin inhibiting angiotensin I-converting enzyme

In order to explore the mechanism underlying the ACE inhibitory activity of the active peptides derived from salmon skin in depth, salmon skin collagen peptides (SSCPs) were produced by the hydrolysis of Atlantic salmon (Salmo salar L.) skin and isolated by reverse-phase liquid chromatography. A total of 13 low-molecular-weight peptides were identified by mass spectrometry and used to analyze the inhibitory activity of angiotensin I-converting enzyme (ACE). Three peptides-Gly-Arg, Arg-Glu-Arg, and Gly-Pro-Arg-exhibited the highest ACE inhibitory activities with IC50 values of 0.73 +/- 0.05, 0.89 +/- 0.06, and 1.05 +/- 0.13 mg/mL, respectively. These ACE inhibitory peptides were quantified, and their potential absorption, distribution, metabolism, excretion, and toxicity were predicted in silico together with two previously identified ACE inhibitory dipeptides Ala-Pro and Val-Arg. The molecular mechanism underlying the interaction between the peptides and ACE was determined using in silico methods, including molecular docking, pharmacophore modeling, and pharmacophore heat maps. The five ACE inhibitory peptides exhibited satisfactory absorption, distribution, metabolism, excretion, and toxicity. They formed hydrogen bonds, ionic bonds, metal-receptor bonds, and hydrophobic bonds with ACE to exert ACE inhibitory effects. Hydrogen bonding was the essential factor influencing ACE inhibitory activity.

Automated summary

The ACE inhibitory peptides derived from salmon skin collagen peptides showed significant ACE inhibitory activity, particularly three peptides with the highest activity. By predicting the potential mechanisms and toxicity of the five ACE inhibitory peptides in vivo, it was found that hydrogen bonding was the key factor influencing ACE inhibitory activity.