Showdomycin, a new nucleoside antibiotic.

The metabolism and inhibitory effects of the carbon-linked nucleoside antibiotic showdomycin were investigated in cell-free preparations of Ehrlich ascites cells. The antibiotic is not a substrate for nucleoside kinase or nucleoside phosphorylase. Showdomycin shows inhibitory effects on certain enzymes in an Ehrlich ascites cell preparation, which are involved in uridine and orotic acid metabolism. It inhibits uridine-5′-monophosphokinase, uridine phosphorylase, and possibly orotidylic acid pyrophosphorylase reactions, but has no effect on the activity of uridine kinase or adenosine phosphorylase. Showdomycin strongly inhibits bovine liver uridine-5′-diphosphate-α-d-glucose dehydrogenase but has no effect on rabbit muscle lactic acid dehydrogenase. The selective inhibition of certain enzymes by showdomycin may be related to the alkylating property of its maleimide structure, which is known to specifically react with sulfhydryl groups.