Synthesis and Immunological Studies of the Lipomannan Backbone Glycans Found on the Surface of Mycobacterium tuberculosis

5 years ago

Synthesis and Immunological Studies of the Lipomannan Backbone Glycans Found on the Surface of Mycobacterium tuberculosis

Siwarutt Boonyarattanakalin, Somsak Ruchirawat, Kanokthip Boonyarattanakalin, Marisa Ponpuak, Niwat Kangwanrangsan, Ratthaphol Charlermroj, Runglawan Chawengkirttikul, Harin Leelayuwapan

Investigations into novel bacterial drug targets and vaccines are necessary to overcome tuberculosis. Lipomannan (LM), found on the surface of Mycobacterium tuberculosis (Mtb), is actively involved in the pathogenesis and survival of Mtb. Here, we report for the first time a rapid synthesis and biological activities of an LM glycan backbone, α(1–6)mannans. The rapid synthesis is achieved via a regio- and stereoselective ring opening polymerization to generate multiple glycosidic bonds in one simple chemical step, allowing us to finish assembling the defined polysaccharides of 5–20 units within days rather than years. Within the same pot, the polymerization is terminated by a thiol-linker to serve as a conjugation point to carrier proteins and surfaces for immunological experiments. The synthetic glycans are found to have adjuvant activities in vivo. The interactions with DC-SIGN demonstrated the significance of α(1–6)mannan motif present in LM structure. Moreover, surface plasmon resonance (SPR) showed that longer chain of synthetic α(1–6)mannans gain better lectin’s binding affinity. The chemically defined components of the bacterial envelope serve as important tools to reveal the interactions of Mtb with mammalian hosts and facilitate the determination of the immunologically active molecular components.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00703

DOI: 10.1021/acs.joc.7b00703