Bio-Inspired Glycan Based Probes for Rapid Detection of TB Infection

用于快速检测结核感染的仿生聚糖探针

• 批准号: 2879762
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2879762
• 关键词: Bio; Inspired; Glycan; Based; Probes

A total of 1.5 million people died from tuberculosis disease in 2020, it is the 13th most frequent cause of death worldwide, and the second largest cause of death by infectious disease behind COVID-19.1 The majority of TB infections are asymptomatic and there is a need to identify latent or nascent infections to prevent transmission and start appropriate treatment quickly. Our goal is to work in collaboration with FluoretiQ Ltd. to develop a new rapid diagnostic tool to aid in this endeavour. Mycobacterium tuberculosis (Mtb) has been shown to interact with a variety of glycans, including the non-mammalian disaccharide trehalose, found in the Mtb cell envelope.2,3 We propose to leverage these interactions in the design and synthesis of a variety of probes consisting of trehalose or analogues of trehalose conjugated to nanomaterial-based sensors, with the aim of achieving selective binding to, and therefore definitive detection of Mtb. Trehalose consists of two alpha,alpha (1-1') linked glucose units, and previous work in the Galan group has achieved the Au(III) catalysed coupling of protected 2-deoxy pyranose hemiacetals into 2,2'-dideoxy trehalose analogues.4 We aim to expand this methodology to accept fully oxygenated substrates in order to access a variety of functionalised trehalose analogues in a convergent fashion. We would like to apply automated synthesis to refine yields with a design of experiments approach, and subsequently synthesise a library of trehalose analogues, with appropriate functionality for conjugation to nano-platforms. This library will include mixed trehaloses (e.g. galactose-glucose and mannose-glucose). These will then be screened for binding to mycobacteria in collaboration with co-workers in the School of Cellular and Molecular Medicine.

2020年共有150万人死于结核病，是全球第13大最常见的死因，也是仅次于COVID-19的第二大传染病死因。我们的目标是与FluoretiQ Ltd.合作开发一种新的快速诊断工具，以帮助这一努力。结核分枝杆菌（Mtb）已被证明与多种聚糖相互作用，包括在Mtb细胞培养物中发现的非哺乳动物二糖海藻糖。2，3我们建议在设计和合成由海藻糖或海藻糖类似物与纳米材料传感器偶联组成的多种探针时利用这些相互作用，目的是实现选择性结合，从而明确检测出结核分枝杆菌。海藻糖由两个α，α（1- 1 '）连接的葡萄糖单元组成，Galan小组先前的工作已经实现了Au（III）催化的受保护的2-脱氧吡喃糖半缩醛偶联成2，2'-双脱氧海藻糖类似物。4我们的目标是扩展这种方法，以接受完全氧化的底物，从而以收敛的方式获得各种功能化海藻糖类似物。我们希望应用自动化合成以通过实验设计方法来改进产率，并随后合成海藻糖类似物的文库，其具有用于缀合至纳米平台的适当功能。该文库将包括混合海藻糖（例如半乳糖-葡萄糖和甘露糖-葡萄糖）。然后将与细胞和分子医学学院的同事合作筛选这些与分枝杆菌结合的抗体。