INHIBITORY EFFECT OF MODIFIED BAFILOMYCINS AND CONCANAMYCINS ON P-TYPE AND V-TYPE ADENOSINE-TRIPHOSPHATASES

Various ATPases have been tested for their sensitivity to naturally oc curring unusual macrolides and their chemically modified derivatives, which are structurally related to bafilomycin A1(1), the first specifi c inhibitor of vacuolar ATPases. The structure-activity study showed t hat in general the concanamycins, 18-membered macrolides, are better a nd more specific inhibitors than the bafilomycins of this class of mem brane-bound ATPases. The additional carbohydrate residue is not respon sible for the improved activity. The importance of an intact hemiketal ring, which is part of an intramolecular hydrogen-bonding network, an d the effects of the size of the macrolactone ring are discussed. The structurally related elaiophylin (13), a C2-symmetric macrodiolide ant ibiotic, proved to be inactive on vacuolar ATPases but still retained its inhibitory effect on P-type ATPases.