INHIBITION OF NA-ATPASE BY THE CARDENOLIDE 6'-O-(E-4-HYDROXYCINNAMOYL) DESGLUCOUZARIN(,K+)

Among the major cardenolides from the milkweed Asclepias asperula, 6'- O-(E-4-hydroxycinnamoyl) desglucouzarin has not been characterized bio chemically. In this study, its binding affinity for a physiological re ceptor, porcine kidney Na+,K+-ATPase, was found to be lower than the o ther cardenolides in this plant. The order of affinities from highest to lowest was: uzarigenin (K-d = 1.05 mu M) = desglucouzarin (K-d = 0. 98 mu M) > uzarin (K-d = 4.0 mu M) > 6'-O-(E-4-hydroxycinnamoyl) desgl ucouzarin (K-d = 16 mu M). The chemical attachment of the 4-hydroxycin namoyl group to the 6'-carbon of desglucouzarin significantly inhibits binding. This agrees with predictions that a 5'-methyl group on carde nolides fits the receptor site optimally for the porcine kidney enzyme . The 4-hydroxycinnamic ester was also found to be fluorescent. (C) 19 98 Academic Press.