Angiotensin I-converting enzyme (ACE), which is a key enzyme of the renin-angiotensin system, is one of target for antihypertensive molecules. Indeed, ACE is well known for its involvement in hypertension which is the main risk factor involved in the development of cardiovascular and kidney diseases and is a major cause of morbidity and mortality. Currently, many pharmacological ACE inhibitors (captopril, lisinopril…) are used for hypertension treatment, but their administration over a long period is associated with some undesirable side effects. Furthermore, there are many publications dealing with antihypertensive peptides from food proteins. ACE-inhibitory peptides, generated by hydrolysis of food proteins, may be a natural alternative to prevent hypertension appearance. However, among the bioactive peptides published in the literature as ACE inhibitors, a very small number really displays an antihypertensive activity in vivo in animals. Moreover, their mechanism of action at the molecular level is still misunderstood.

The objective of our work was to characterize the molecular interactions between ACE and some peptides described as ACE-inhibitors, which have or not a true antihypertensive activity in vivo.

For this purpose, a methodology already developed in our teams was employed (Zidane et al., 2013). It is based on the use, for the first time, of Biacore^® technology (SPR). This real time technology provides some important molecular information such as the rate constants of association and dissociation, the stoichiometry and the site of the interaction on ACE. In our study, the direct interaction between ACE and inhibitors (without substrate or ligand) showed dissociation constants (K_D) of the same order of magnitude as IC₅₀. Moreover, the formed ACE-inhibitor complexes are unstable. Given these results, it is difficult to attribute significant antihypertensive effect demonstrated in vivo for these peptides (for example IPP, VPP) to the only ACE inhibition.