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红细胞和通过细胞粘附引起的，红细胞粘附到宿主的细胞上，衬在血管上。玫瑰花结形成和细胞粘附都阻止了大脑毛细血管周围的红细胞对氧气的适当运输，并导致阻塞，损害大脑，这通常是致命的。该项目将从一个新的带负电荷的碳水化合物的半合成文库中鉴定出最简单的片段，这些片段能够破坏玫瑰花结和细胞粘附，同时最大限度地减少/消除任何潜在的副作用。这将提供所需的最小结构的信息，允许进行廉价的分子化学合成。该项目将最终导致开发新的药剂，这是迫切需要的，因为目前正在管理的药物出现耐药性。

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.