Main content area

Synthesis of synthetic mannan backbone polysaccharides found on the surface of Mycobacterium tuberculosis as a vaccine adjuvant and their immunological properties

Wattanasiri, Chakree, Paha, Jiraporn, Ponpuak, Marisa, Ruchirawat, Somsak, Boonyarattanakalin, Siwarutt
Carbohydrate polymers 2017 v.175 pp. 746-755
Mycobacterium tuberculosis, adjuvants, immune response, inflammasomes, mannose, polymerization, polysaccharides, synthesis, transcription factor NF-kappa B, tuberculosis
Surface components of Mycobacterium tuberculosis (Mtb) play crucial roles in modulating host immune responses. Thorough understandings of immunological properties of the Mtb’s surface components are essential for the development of tuberculosis treatment and prevention. Unfortunately, the accessibility to the molecules on the surface of Mtb is limited by the structural complexity due to their various macromolecular nature and the hazard of culturing Mtb. In this study, we reveal a practical synthesis of lipomannan (LM) backbone polysaccharides – the core glycans found on Mtb’s surface. A rapid synthetic approach based on a controlled polymerization was developed for the chemical synthesis of mannopyranans, the core structure of LM. The size of the LM glycans can be controlled by using specific monomer concentrations in addition to stereo- and regioselectivity derived from the versatile tricyclic orthoester mannose monomer. The immunological properties of the synthesized mannopyranans were investigated and their adjuvant potential was revealed. The adjuvanticity mechanism of the synthetic mannopyranans appears to involve the NF-κB and inflammasome pathways.