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

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.