THE IMPORTANCE OF THE HYDROXYL MOIETIES FOR INHIBITION OF THE CA2-ATPASE BY TRILOBOLIDE AND 2,5-DI(TERT-BUTYL)-1,4-BENZOHYDROQUINONE()

Trilobolide and 2,5-di(tert-butyl)1,4-benzohydroquinone (BHQ) are pote nt inhibitors of the Ca2+-ATPase of skeletal muscle sarcoplasmic retic ulum. Desoxytrilobolide and 2,5-di(tertbutyl)-1 ,4-diacetylphenol (ace tyl-BHQ) have much lower potencies than their parent compounds and 2,5 -di(tert-butyl)-1,4-benzoquinone (BQ) has no effect on ATPase activity . Studies using the ATPase labelled with 4-nitrobenzo-2-oxa-1,3-diazol e (NBD) suggest that both trilobolide and BHQ bind more strongly to th e E2 conformation of the ATPase than to the E1 conformation. Desoxytri lobolide, acetyl-BHQ and BQ have little effect on the E1/E2 equilibriu m. Studies with mixtures of trilobolide and desoxytrilobolide suggest that the inactive derivatives are unable to bind to the ATPase. (C) 19 94 Academic Press, Inc.