The main objective of the work was to develop a novel analytical tool, incorporating EVA-biosensor technology, for the diagnosis of TB, and this was achieved in three parts. The first target of the first part was the total synthesis of two novel diastereomers of α-methyl-trans-cyclopropane mycolic acids (I) and (II) present in the cell wall of Mycobacterium avium complex and Mycobacterium Kansasii. The second target of the first part was the synthesis of four cord factors as derivatives of compounds (I) and (II), in order to understand their interaction with the immune system and for use in biosensor technologies, as well as ELISA assays, for the diagnosis of TB. The synthesized cord factors were TDM (III), TMM (IV), TDM (V) and TMM (VI).
The second part of this project was to synthesize thiolated derivatives of α-mycolic acids which were the disulfide (VII) and free thiol (VIII). These compounds would eventually be bound to a gold surface and their activities against tuberculosis antibodies tested. This will be used to develop a new biosensor technique for detection of TB.The third part concerned the application of the synthetic molecules in an exploratory biological investigation for the development of a rapid and accurate TB diagnostic. Three novel synthetic cord factors as synthetic antigens were used on a novel biosensor platform, the EVA -Evanescent Biosensor Technology, with TB positive and negative sera. These antigens showed significant sensitivities and specificities by this technique.