STRUCTURAL STUDIES OF TRYPANOSOMAL GLYCOLYTIC ENZYMES

锥虫属和锥虫属的寄生锥虫 利什曼原虫是各种严重的 破坏性疾病。其中最致命的一种疾病是 非洲昏睡病，其病原体是锥虫 布鲁克西。选择性抑制锥虫体糖酵解的化合物 酶比等效人糖酵解酶要好 有效的新药设计的良好起点 关注锥虫疾病。我们建议采用一种循环 三维结构测定与分子结构的研究进展 在寻找这类化合物的过程中进行建模。这项提议涉及到 药物设计周期的结构决定方面 与锥体糖酵解酶中的两种有关， 甘油醛-3-磷酸脱氢酶(GAPDH)和醛缩酶。

The parasitic trypanosomal species of the genera Trypanosoma and Leishmania are the causative agents of a wide variety of severely destructive diseases. One of the deadliest of these diseases is African sleeping sickness, the causative agent of which is Trypanosoma bruccei. Compounds which selectively inhibit trypanosomal glycolytic enzymes over the equivalent human glycolytic enzymes would be an excellent starting point for the design of new drugs effective in attentuating trypanosomal diseases. We propose to employ a cyclic process of three-dimensional structure determination and molecular modelling in the search for such compounds. This proposal concerns the structural determination aspect of the drug design cycle pertaining to two of these trypanosomal glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase.