Membrane-specific inhibitors of the bovine heart mitochondrial ATPase.

New cationic inhibitors of the bovine heart mitochondrial ATPase have been synthesized by quaternizing 1-dansylamido-3-dimethypropylamine with decyl and hexadecyl iodides. These ligands are unique in their mode of action because they inhibit the submitochondrial membrane-associated forms of the enzyme more potently than the soluble form of the enzyme (F1). Derivatives prepared with propyl or hexyl iodides are weak inhibitors and exhibit little affinity for submitochondrial membranes particle. The inhibitory effectiveness of these derivatives measured either in the direction of ATP synthesis or ATP hydrolysis results from efficient insertion into the membrane. Other inhibitory organic cations such as the 3:1 4,7-diphenyl-1,10-phenanthroline-ferrous chelate and alkyl guanidines inhibit both the membrane-associated and soluble ATPase comparably.