A POTENT SPECIFIC INHIBITOR OF 6-PHOSPHOGLUCONATE DEHYDROGENASE OF CRYPTOCOCCUS-NEOFORMANS AND OF CERTAIN OTHER FUNGAL ENZYMES

A particular lot of the zwitterionic buffer, 2(N-morpholino) ethane su lfonic acid (MES), contained a contaminant that inhibited a number of fungal NADP-dependent dehydrogenases. Enzymes that were particularly s ensitive include 6-phosphogluconate dehydrogenases from Cryptococcus n eoformans and Schizophyllum commune and glucose-6-phosphate dehydrogen ase from Schizophyllum commune. A number of NADP-dependent dehydrogena ses of animal origin were tested and all were completely insensitive t o inhibition except for rat liver 6-phosphogluconate dehydrogenase, wh ich was 10-fold less sensitive than the Cryptococcal enzyme. The patte rn of inhibition in all cases was linear competitive versus NADP. The inhibitor has been purified and identified as an ethylenesulfonic acid oligomer. This inhibitor holds promise as a model compound for the de velopment of a specific antifungal agent.