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.
Department of Chemistry, City University of New York Medical School, City College of City University of New York, New York 10031.
S
S
Merali
Y
Y
Zhang
D
D
Sloan
S
S
Meshnick
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