Use of Transporters to Selectively Deliver Agents to Trypanosomes

使用转运蛋白选择性地将药剂递送至锥虫

• 批准号: G0500569/1
• 负责人: Ian Gilbert
• 金额: $ 31.85万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0500569%2F1
• 关键词: Use; Transporters; Selectively; Deliver; Agents

Human African trypanosomiasis (HAT), more commonly known as sleeping sickness is prevalent in sub-Saharan Africa and is inevitably fatal unless treated. It is caused by single-celled parasites, which live in the blood stream and eventually invade the brain. The current drugs available to treat the disease are unsatisfactory, due to issues such as toxicity, resistance, difficulty in administration of the drugs, lack of efficacy and cost. In this basic science proposal we aim to start the development of new drugs. The parasites which cause HAT require nutrients from the human host for their survival. To take up these nutrients, they have transporters in their cell membranes. Some of these transporters are very different from those found in human cell membranes. One particular transporter, usually involved in carrying important chemicals called purines into cells, can be tricked into carrying other classes of molecules (transporter motifs), which are not carried by mammalian purine transporters. We aim to develop new classes of drugs to treat HAT by attaching compounds that will kill parasites to these transporter motifs. These compounds should then selectively kill the parasites. The project will consist of design and preparation of these compounds, evaluation and studying how the compounds work.

人类非洲锥虫病(HAT)，通常被称为昏睡病，在撒哈拉以南非洲流行，除非得到治疗，否则不可避免地会致命。它是由单细胞寄生虫引起的，这种寄生虫生活在血液中，最终入侵大脑。目前治疗该病的药物并不令人满意，原因是毒性、耐药性、给药困难、缺乏疗效和成本等问题。在这项基础科学提案中，我们的目标是启动新药的开发。引起HAT的寄生虫需要来自人类宿主的营养才能生存。为了吸收这些营养物质，它们的细胞膜中有转运体。其中一些转运蛋白与人类细胞膜中发现的转运蛋白非常不同。一种特殊的转运体，通常参与将称为嘌呤的重要化学物质运送到细胞中，可以被诱骗携带其他类别的分子(转运体基序)，而哺乳动物的嘌呤转运体不会携带这些分子。我们的目标是开发治疗HAT的新型药物，方法是将杀死寄生虫的化合物附加到这些转运蛋白基序上。然后，这些化合物应该有选择地杀死寄生虫。该项目将包括这些化合物的设计和制备、评估和研究这些化合物的工作原理。