Rapid Synthesis Of Mycobacterial Mannan Polysaccharide With Alkyne Terminated Linker

Recently, we have found that the synthetic polysaccharides, alpha(1,6)polymannans, derived from the surface molecules of Mycobacterium tuberculosis (Mtb), have potent immune modulatory properties. In the quest to increase the potency of this polysaccharide, a dimerization on the reducing end of the polymer molecules, that would yield an alpha(1,6)polymannan dimer, is revealed here. The dimer of the polysaccharide would interact stronger with mammalian immune receptors through more multivalent bindings. Thus, we set out to synthesize the dimerized alpha(1,6)polymannan relying on a cross coupling of the functionalized polysaccharide at its reducing end. A conjugated alpha(1,6)polymannan with an alkyne linker was achieved in a single chemical transformation, using a tricyclic mannosyl orthoester as a monomer. The synthetic approach relies on regio- and stereocontrolled polymerization. The terminal alkyne of conjugated polymannan facilitates a self-cross-coupling reaction, providing a dimer of alpha(1,6)polymannan. The dimer of the polysaccharide may be a more potent immune modulatory agent due to the more multivalency binding with human immune receptors such as DC-SIGN and mannose receptor in human immune system. This target molecule may serve as a vaccine adjuvant by increasing immune responses toward a vaccine antigen.