Synthesis of a Fluorescent,Cardioactive Analogue Digoxin

Abstract

In order to develop a better understanding of the mechanism of action of the cardioactive steroid glycoside digoxin, we have synthesized a fluorescent analogue of this drug which retains biological activity. Fluoroscein isothiocyanate has been coupled to digoxin via an ethyl lysine bridge, after mild periodate oxidation of the terminal glycase moiety. The conjugate can displace oubain from the plasma membrane digoxin receptor, Na⁺/K⁺ ATPase and can itself be displaced by native digoxin. The structure of the conjugate based on FAB mass spectroscopy is presented.