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，在人类中引起许多重要疾病，困扰着全世界超过1200万人。目前，很少有药物针对这些寄生虫引起的传染病阶段。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，这似乎对感染性很重要。在这项提案中，我们将研究这种糖聚合物是如何制成的，确定参与其合成的酶，并开发新的化学工具，用于产生高度特异性的利什曼原虫糖生物合成抑制剂。该项目将为人类病原体的重要群体的生存和感染性所必需的过程提供新的见解，并导致开发具有抗寄生虫活性的新型酶抑制剂。

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.