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molecule as a prototype, captopril was designed with a car-boxyl group on a proline and a thiol group was introduced to enhance the binding to the zinc ion of ACE. The important binding points at the active site of ACE are thought to be an arginine residue, which provides a cationic site that attracts a carboxylate ion, and a zinc ion, which can polarize a carbonyl group of an amide function to make it more susceptible to hydrolysis. Hydrophobic pockets lie between these groups in the active site, as does a functional group that forms a hydrogen bond with an amide carbonyl. Figure 18.5 shows the hypothetical binding of captopril in the active site of ACE.

Lisinopril. Lisinopril, 1-[N2-[S-1-carboxy-3-phenyl-propyl]-l-lysyl]-l-proline dihydrate (Prinivil, Zestril), is a lysine derivative of enalaprilat, the active metabolite of enalapril. Like all ACE inhibitors, it is an active site-directed inhibitor of the enzyme, with the zinc ion used in an effective binding interaction at a stoichiometric ratio of 1:1. The pharmacological effects of lisinopril are similar to those of captopril and enalapril.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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