Affinity Purification and Molecular Characterization of Angiotensin-Converting Enzyme (ACE)-Inhibitory Peptides from Takifugu flavidus

  • Mar Drugs. 2023 Sep 29;21(10):522. doi: 10.3390/md21100522.
Yongchang Su  1  2 ,  Shicheng Chen  3 ,  Shuji Liu  2 ,  Yin Wang  2 ,  Xiaoting Chen  2 ,  Min Xu  2 ,  Shuilin Cai  2 ,  Nan Pan  2 ,  Kun Qiao  2 ,  Bei Chen  2 ,  Suping Yang  1 ,  Zhiyu Liu  2
Affiliations
  • 1. College of Chemical Engineering, Huaqiao University, Xiamen 361021, China.
  • 2. Key Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China.
  • 3. Medical Laboratory Sciences Program, College of Health and Human Sciences, Northern Illinois University, DeKalb, IL 60015, USA.
PMID: 37888457 DOI: 10.3390/md21100522
Abstract

An affinity chromatography filler of CNBr-activated Sepharose 4B-immobilized ACE was used to purify ACE-inhibitory peptides from Takifugu flavidus protein hydrolysate (<1 kDa). Twenty-four peptides with an average local confidence score (ALC) ≥ 80% from bounded components (eluted by 1 M NaCl) were identified by LC-MS/MS. Among them, a novel peptide, TLRFALHGME, with ACE-inhibitory activity (IC50 = 93.5 µmol·L-1) was selected. Molecular docking revealed that TLRFALHGME may interact with the active site of ACE through H-bond, hydrophobic, and electrostatic interactions. The total binding energy (ΔGbinding) of TLRFALHGME was estimated to be -82.7382 kJ·mol-1 by MD simulations, indicating the favorable binding of peptides with ACE. Furthermore, the binding affinity of TLRFALHGME to ACE was determined by surface plasmon resonance (SPR) with a Kd of 80.9 µmol, indicating that there was a direct molecular interaction between them. TLRFALHGME has great potential for the treatment of hypertension.

Keywords
ACE-inhibitory activity; Takifugu flavidus; affinity purification; antihypertensive effect; molecular docking.
Products