Molecular Pharmacology, Vol 10, 140-145, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Dihydropteroate Synthetase from Plasmodium berghei: Isolation, Properties, and Inhibition by Dapsone and Sulfadiazine

¹ Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32601

Dihydropteroate synthetase, which catalyzes the condensation of 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphate and p-aminobenzoic acid to form dihydropteroic acid, has been isolated from cells of the rodent malarial organism Plasmodium berghei; some of its properties are described. The optimum pH for enzyme activity was found to be 8.5. The apparent Michaelis constants for p-aminobenzoic acid and the hydroxymethyldihydropteridine pyrophosphate were found to be 2.8 µM and 1.4 µM, respectively. Both 4,4'-diaminodiphenylsulfone (I₅₀ = 89 µM) and sulfadiazine (I₅₀ = 180 µM) were effective inhibitors of enzyme activity. The inhibition of the enzyme by these drugs correlated with their activity in vivo against P. berghei infections.

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ACKNOWLEDGMENT The authors were greatly aided in the preparation of this paper by discussion with Dr. Betty P. Vogh.