Transport of traditional Chinese pimple milk-derived angiotensin-converting enzyme (ACE) inhibitory peptides across a Caco-2 cell monolayer and their molecular recognition with ACE

A Caco-2 cell monolayer was used to predict the transport of bioactive peptides in human intestine. Three di-peptides from the digest of traditional Chinese pimple milk that were transportable across the monolayer with high content and strong ACE inhibitory ability were determined to be ValPro, Lys-Pro and Tyr-Pro. The same order of magnitude for apparent permeability coefficients (1.8×10 -6 , 2.2×10 -6 and 2.6×10 -6 cm·s -1 , respectively) revealed the similar transport capacity of the three peptides. For K m values, Lys-Pro (24.4 mM) and Tyr-Pro (17.5 mM) exhibited higher affinity toward the transport compared with Val-Pro (42.7 mM). Automated molecular docking showed a lower affinity energy for the best pose of Lys-Pro (-47.30 kJ/mol) at the ACE active site than for those of Val-Pro (-34.74 kJ/mol) and Tyr-Pro (-32.78 kJ/mol). The interactions, including H-bonds, hydrophobic, hydrophilic and electrostatic interactions, as well as the interaction with Zn 2+ , were responsible for the binding of inhibitory peptides to ACE.