Inhibition of Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.
A new reversed-phase high-pressure liquid chromatography assay procedure for dihydropteroate synthetase (DHPS) that involves the elution of the enzyme incubation solution with a series of three solvents of decreasing polarity (ammonium phosphate buffer, 10% methanol, and 50% methanol) was designed. By this procedure DHPS was detected in Escherichia coli and Pneumocystis carinii with specific activities of 450 and 14 U/mg, respectively. A comparison of the effects of five sulfa drugs on P. carinii DHPS activity revealed that dapsone is the most potent of these drugs.
Merali
S
S
Department of Chemistry, City University of New York Medical School, City College of City University of New York, New York 10031.
Zhang
Y
Y
Sloan
D
D
Meshnick
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology; D005656:Fungal Proteins / Q000302:isolation & purification; D008297:Male; D010766:Phosphorylation; D011010:Pneumocystis / Q000187:drug effects / Q000201:enzymology*; D011622:Pterins / Q000138:chemical synthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D014166:Transferases / Q000037:antagonists & inhibitors*
D005656:Fungal Proteins; D011622:Pterins; D013449:Sulfonamides; D013450:Sulfones; D014166:Transferases; D004094:Dihydropteroate Synthase