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

Abstract

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 α-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 α-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 α-amylase active site and the K residue in peptide formed intensive H-bonds and electrostatic interactions with catalytic triad Asp₁₉₇ - Asp₃₀₀ - Glu₂₃₃. Another peptide APFPLR showed different poses in inhibiting ACE, α-amylase and lipase, and it formed direct interactions to lipase catalytic residues Phe₇₇ & His₂₆₃.

Keywords: ACE; Inhibition; Lipase; Peptides; α-Amylase.