AIDS OPPORTUNISTIC INFECTIONS DRUG DESIGN

卡氏肺孢子虫肺炎（PCP）是导致 艾滋病患者。 同样，弓形虫，一种普遍存在的 寄生原生动物，造成重大的发病率和死亡率， 艾滋病患者。 卡氏肺孢子虫和弓形虫目前的治疗方案。 弓形虫感染通常会产生严重的副作用， 停止治疗。 人们普遍认为， 迫切需要新的作用机制来治疗 五氯苯酚和弓形虫病。 我们已经启动了两种结构药物 设计程序，使改进的抑制剂和有毒底物的T。 弓形虫次黄嘌呤-鸟嘌呤磷酸核糖基转移酶（HGPRT）和 尿嘧啶磷酸核糖转移酶（UPRT）、T.二氢叶酸弓形虫 还原酶-胸苷酸合酶（DHFR-TS）和卡氏肺吸虫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.