Synthetic Lipomannan Glycan Microarray Reveals the Importance of α(1,2) Mannose Branching in DC-SIGN Binding

Lipomannan (LM), a glycophospholipid found on the cell surface of mycobacteria, involves the virulence and survival in host cells. However, there is little to no information on how exactly mannan alignment, including the number of mannose units and the branched motif of LM, affects protein engagement during host-pathogen interactions. In this study, we synthesized the exact substructures of the LM glycans that consist of an α(1,6) mannan core, with and without the complete α(1,2) mannose branching, and comparatively studied their protein-carbohydrate interactions. The synthetic LM glycans were equipped with a thiol linker for immobilizations on the surfaces of microarrays. As per our findings, the presence of the branching α(1,2) mannose on the LM glycans increases their binding toward the dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin receptor. An increase in the number of mannose units on the glycans also increases the binding with the mannose receptor. Thus, the set of synthetic glycans can serve as a useful tool to study the biological activities of LM and can provide a better understanding of host-pathogen interactions.