Novel semi-synthetic carbohydrates as potential therapeutics for severe malaria

严重疟疾是一种每年造成数百万人死亡的疾病，特别是在发展中国家，造成广泛的痛苦和经济损失。严重的疟疾是由被寄生虫感染的红细胞聚集成玫瑰花和细胞粘附引起的，红细胞附着在宿主的细胞上，排列在血管里。玫瑰花结的形成和细胞粘附都阻碍了大脑毛细血管周围的红细胞对氧气的适当运输，并导致堵塞，损害大脑，这通常是致命的。该项目将从一种新颖的带负电荷的半合成碳水化合物库中识别最简单的片段，这些片段能够破坏结簇和细胞粘附，同时最大限度地减少/消除任何潜在的副作用。这将提供有关所需最小结构的信息，使分子的廉价化学合成得以进行。该项目最终将导致开发新的药物制剂，这是迫切需要的，因为目前正在使用的药物出现了耐药性。

Severe malaria is a disease that kills millions every year, especially in developing nations, resulting in widespread suffering and economic damage. Severe malaria is caused by both the aggregation of red blood cells infected by the parasite into rosettes and via cytoadherence, the attachment of red blood cells to the cells of the host, lining the blood vessels. Rosette formation and cytoadherence both prevent proper transport of oxygen by the red blood cells around the capilaries of the brain and causes blockages, damaging the brain, and this is often fatal. This project will identify the simplest fragments, from a novel semi-synthetic library of negatively charged carbohydrates, that are able to disrupt rosetting and cytoadherence while minimising/eliminating any potential side-effects. This will provide information concerning the minimum structures required, allowing cheap, chemical synthesis of the molecules to be undertaken. This project will ultimatley lead to the development of new pharmaceutical agents, which are urgently needed, as resistance emerges to the drugs being administered currently.