Targeted Catalytic Inactivation of Angiotensin Converting Enzyme by Lisinopril-Coupled Transition-Metal Chelates

摘要: A series of compounds that target reactive transition-metal chelates to somatic angiotensin converting enzyme (sACE-1) have been synthesized. Half-maximal inhibitory concentrations (IC50) and rate constants for both inactivation cleavage full-length sACE-1 determined evaluated in terms metal chelate size, charge, reduction potential, coordination unsaturation, coreactant selectivity. Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic (NTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic (DOTA), tripeptide GGH were linked the lysine side chain lisinopril by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride/N-hydroxysuccinimide coupling. The resulting amide-linked chelate–lisinopril (EDTA–lisinopril, NTA–lisinopril, DOTA–lisinopril, GGH–lisinopril) conjugates used form complexes with iron, cobalt, nickel, copper, such could mediate localization sACE-1. ACE act...