Structure-Activity Relationship of Novel ACE Inhibitory Undecapeptides from Stropharia rugosoannulata by Molecular Interactions and Activity Analyses

Undecapeptide is the central peptide molecule in the peptide base material of Stropharia rugosoannulata, and angiotensin-converting enzyme (ACE) plays a crucial role in hypertension. To fully explore the interaction mechanism and ACE-inhibitory activity of long-chain peptides from Stropharia rugosoannulata, the binding conformations of twenty-seven undecapeptides with the ACE receptor were revealed by molecule docking. The undecapeptide GQEDYDRLRPL with better receptor binding capacity and higher secondary mass spectral abundance was screened. All amino acid residues except proline in GQEDYDRLRPL interacted with the ACE receptor. GQEDYDRLRPL interfered with the receptor's overall structure, with significant fluctuations in amino acid residues 340-355, including two residues in the receptor's active pockets. The binding constants of GQEDYDRLRPL to the ACE receptors were at the mu M level, with a kinetic binding constant of 9.26 x 10(-7) M, which is a strong binding, and a thermodynamic binding constant of 3.06 x 10(-6) M. Intermolecular interaction were exothermic, enthalpy-driven, and specific binding reactions. GQEDYDRLRPL had an IC50 value of 164.41 mu mol/L in vitro and superior antihypertensive effects at low-gavage administration in vivo. Obtaining information on the interaction mechanism of ACE-inhibitory undecapeptides from S. rugosoannulata with the ACE receptor will help to develop and utilize ACE inhibitors of natural origin.