LIPIDS OF LEISHMANIAS AND TRYPANOSOMES

这个项目的长期目标是确定和研究 控制利什曼病和黑热病的新化疗方法 美国具有重大医学意义的锥虫感染， 通过利用知识，脂类生物化学的各个方面 负责任的锥虫鞭毛虫的特征是 真菌和其他植物，而不是脊椎动物。最直接的 实现这一目标的具体目标是调查： A)甾醇、磷脂和鞘糖脂的生物化学 具有代表性的利什曼原虫种类和生活史阶段 克氏锥虫菌株，b)生物化学的扰动， 以及针对特定药物引起的生长发育障碍 酶反应，以及c)MOST的作用机制 这些药物的有效性。生命周期阶段需要培养 在暴露于药物和放射的组织细胞内和之外--以及 稳定的同位素示踪剂及其对生长和 用人口计数和脂类评估脂类代谢 使用色层分析(CC、TLC、HPLC、GLC)，以及 光谱分析(GC/MS、~1H和~(13)C核磁共振、UV/Vis、液体闪烁) 方法论。通过这些手段，活跃在酶反应上的药物 利什曼原虫和锥虫所特有的，或具有 与人类的类似反应不同的是， 以及它们对寄生虫的选择性毒性和 用于建立宿主组织细胞。

The long term objective of this project is to identify and to study novel chemotherapeutic approaches to the control of leishmanial and American trypanosomal infections of substantial medical importance, by exploiting knowledge that aspects of the lipid biochemistry of the responsible trypanosomatid flagellates are characteristic of fungi and other plants and not of vertebrates. The immediate specific aims to realize this objective are to investigate the: a) sterol, phospholipid and glycosphingolipid biochemistry of the life-cycle stages of representative leishmania species and Trypanosoma cruzi strains, b) perturbations of that biochemistry, and impairment of growth, cause by drugs targeted to specific enzymatic reactions, and c) mechanisms of action of the most effective of those drugs. Life-cycle stages are to be cultured within and without tissue cells exposed to drugs and radio- and stable isotopic tracers, and the consequences to growth and to lipid metabolism assessed by population enumeration, and by lipid analyses employing chromatographic (CC, TLC, HPLC, GLC), and spectrometric (GC/MS, 1H & 13C NMR, UV/VIS, liquid scintillation) methodologies. By these means, drugs active on enzymatic reactions unique to leishmanias and trypanosomes, or with properties different from those of analogous reactions in man, are to be identified, and their selective toxicities for the parasites and for host tissue cells established.