Polysaccharide biosynthesis as a new drug target in Leishmania parasites

利什曼原虫是一种原生动物寄生虫，会导致人类患上许多重要疾病，全球有1200多万人深受其害。目前几乎没有针对导致这些寄生虫阶段的传染病的药物。我们最近发现，利什曼原虫在感染哺乳动物细胞时，会积累一种非常不寻常的糖聚合物，这似乎对传染性很重要。在这项计划中，我们将研究这种糖聚合物是如何制造的，鉴定参与其合成的酶，并开发新的化学工具来产生高度特异的利什曼原虫糖生物合成抑制剂。该项目将提供对一组重要的人类病原体的生存和传染性至关重要的过程的新见解，并导致具有抗寄生虫活性的新型酶抑制剂的开发。

Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involved in its synthesis and develop new chemical tools for generating highly specific inhibitors of Leishmania sugar biosynthesis. This project will provide new insights into processes that are essential for the survival and infectivity of an improtant group of human pathogens, and lead to the development of new classes of enzyme inhibitors with anti-parasite activity.