Conformation and macromolecular interaction of ACE inhibitors enalapril and lisinopril by NMR

Abstract The solution conformation of the angiotensin-converting enzyme (ACE) inhibitors enalapril and lisinopril was investigated by NMR spectroscopy. Proton resonances were unambiguously assigned by 2D-COSY and NOESY experiments and the results indicate that in DMSO-d 6 solution both compounds exist as cis-trans isomers. The conformation of the two drugs in lipid bilayers was also investigated. In DMSO-d 6 , both molecules adopt an extended backbone conformation, whereas in lipid bilayers, enalapril folds about the backbone, while lisinopril remains in extended conformation. The interaction studies on enalapril with bovine serum albumin (BSA) indicate a weak, hydrophobic binding involving the aromatic ring. In BSA, enalapril is partially folded about the γ-phenylbutyrate moiety. The biological activity of the two ACE inhibitors is discussed on the basis of NMR results.