AIDS OPPORTUNISTIC INFECTIONS DRUG DESIGN

卡氏肺孢子虫肺炎(PCP)是卡氏肺孢子虫肺炎的主要杀手 艾滋病患者。同样，弓形虫，一种普遍存在的 寄生原生动物，在 艾滋病患者。目前对卡氏肺孢子虫和T。 弓形虫感染通常会产生严重的副作用，导致 停止治疗。人们普遍认为，新药具有 迫切需要新的作用机制来治疗 五氯联苯和弓形虫病。我们已经推出了两种基于结构的药物 设计方案以制造改良的T。 刚地龙次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(HGPRT)和 尿嘧啶磷酸核糖转移酶(UPRT)，弓形虫二氢叶酸 还原酶胸苷合成酶(DHFR-TS)和卡氏肺孢子虫DHFR。

Pneumocystis carinii pneumonia (PCP) is the leading killer of patients with AIDS. Similarly, Toxomplasma gondii, a pervasive parasitic protozoan, causes significant morbidity and mortality among AIDS patients. Current treatment regimens for both P. carinii and T. gondii infections often produce severe side effects, leading to the cessation of therapy. It is widely recognized that new drugs having novel mechanisms of action are urgently needed for the treatment of PCP and toxoplasmosis. We have initiated two structure-based drug design programs to make improved inhibitors and toxic substrates of T. gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and uracil phosphoribosyltransferase (UPRT), T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS) and P. carinii DHFR.