Interactions of C. frondosa-derived inhibitory peptides against angiotensin I-converting enzyme (ACE), α-amylase and lipase

The study illustrates the molecular mechanisms by which marine-derived peptides exhibited different structures and inhibition functions to concurrently inhibit multiple enzymes involved in chronic diseases. Peptides (2 mg/mL) exhibited inhibition against angiotensin-converting enzyme (ACE, inhibition of 52.2-78.8%), pancreatic alpha-amylase (16.3-27.2%) and lipase (5.3-17.0%). Further in silico analyses on physiochemistry, bioactivity, safety and interaction energy with target enzymes indicated that one peptide could inhibit multiple enzymes. Peptide FENLLEELK potent in inhibiting both ACE and alpha-amylase showed different mechanisms: it had ordered extended structure in ACE active pocket with conventional H-bond towards Arg522 which is the ligand for activator Cl, while the peptide folded into compact "lariat" conformation within alpha-amylase active site and the K residue in peptide formed intensive H-bonds and electrostatic interactions with catalytic triad Asp(197) - Asp(300) - Glu(233). Another peptide APFPLR showed different poses in inhibiting ACE, alpha-amylase and lipase, and it formed direct interactions to lipase catalytic residues Phe(77) & His(263).