title: Active site-directed alkylation of Na+-K+-ATPase by digitalis sulphonate derivatives of different lipophilicity.
abstract: 1 Sulphonate derivatives of k-strophanthidin and digitoxigenin were tested as active site-directed labels of Na+-K+-adenosine triphosphatase (Na+-ATPase) from guinea-pig heart. 2 Lipophilicity ranged between P = 93 for strophanthidin-3-tosyloxy-acetate (STA) and P = 3028 for digitoxigenin-3-tosyloxy-acetate (DTA). 3 Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+-K+-ATPase inhibition varied appreciably (82% and 35% respectively). 4 It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+-K+-ATPase.
mesh_terms: D000478:Alkylation; D000818:Animals; D001665:Binding Sites; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D050356:Lipid Metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012995:Solubility; D013327:Strophanthidin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004073:Digitoxigenin; D013327:Strophanthidin; C030160:digitoxigenin-3-tosyloxyacetate; C030172:strophanthidin-3-tosyloxyacetate; D000254:Sodium-Potassium-Exchanging ATPase