𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐀𝐂𝐄𝐢 (A) The natural peptide SQ 20881 (sequence EWPRPQIPP), discovered in Bothrops jararaca venom, is an inhibitor of ACE, inducing a drop in blood pressure. Squibb company synthetized a derivative which led, after optimization, to the captopril (1981). Because of the side effects of the thiol group, Merck replaced the latter with a carboxylate, resulting in the enalaprilat molecule (1985). However, as this modification resulted in the loss of oral bioavailability, the esterification of the enalaprilat was considered by Merck to solve the problem successfully and created the enalapril (1985). (B) Interaction between captopril and ACE. By preventing the binding of the inert Angiotensin I to ACE, captopril inhibits the formation of Angiotensin II.
