Queener S F
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202-5120.
J Protozool. 1991 Nov-Dec;38(6):154S-157S.
Dihydrofolate reductase was obtained from Pneumocystis carinii isolated from heavily infected lungs of female Sprague-Dawley rats infected by transtracheal inoculation. The enzyme differed significantly from other forms of dihydrofolate reductase in response to KCl and to antifolate drugs. Dihydrofolate reductase from P. carinii was used to assess activity of analogs of pyrimethamine, methotrexate, and trimetrexate. One pyrimethamine analog was selective for P. carinii dihydrofolate reductase; potency was in the micromolar range. In contrast, 21 methotrexate analogs and 2 trimetrexate analogs were selective for P. carinii dihydrofolate reductase; potencies for these were in the nanomolar range.
二氢叶酸还原酶是从经气管接种感染的雌性斯普拉格-道利大鼠严重感染的肺中分离出的卡氏肺孢子虫中获得的。该酶在对氯化钾和抗叶酸药物的反应方面与其他形式的二氢叶酸还原酶有显著差异。卡氏肺孢子虫的二氢叶酸还原酶被用于评估乙胺嘧啶、甲氨蝶呤和三甲曲沙类似物的活性。一种乙胺嘧啶类似物对卡氏肺孢子虫二氢叶酸还原酶具有选择性；效力在微摩尔范围内。相比之下，21种甲氨蝶呤类似物和2种三甲曲沙类似物对卡氏肺孢子虫二氢叶酸还原酶具有选择性；它们的效力在纳摩尔范围内。
