Immune Effect Regulated by the Chain Length: Interaction between Immune Cell Surface Receptors and Synthetic Glycopolymers

Glycopolymer-based drugs for immunotherapy have attracted increasing attention because the affinity between glycans and proteins plays an important role in immune responses. Previous studies indicate that the polymer chain length influences the affinity. In the studies on enhancing the immune response by glycans, it is found that both oligosaccharides and long-chain glycopolymers work well. However, there is a lack of systematic studies on the immune enhancement effect and the binding ability of oligomers and polymers to immune-related proteins. In this paper, to study the influence of the chain length, glycopolymers based on N-acetylglucosamine with different chain lengths were synthesized, and their interaction with immune-related proteins and their effect on dendritic cell maturation were evaluated. It was proved that compared with l-glycopolymers (degree of polymerization (DP) > 20), s-glycopolymers (DP < 20) showed better binding ability to the dendritic cell-specific ICAM-3-grabbing nonintegrin protein and the toll-like receptor 4 and myeloid differentiation factor 2 complex protein by quartz crystal microbalance and molecular docking simulation. When the total sugar unit amounts are equal, s-glycopolymers are proved to be superior in promoting dendritic cell maturation by detecting the expression level of CD80 and CD86 on the surface of dendritic cells. Through the combination of experimental characterization and theoretical simulation, a deep look into the interaction between immune-related proteins and glycopolymers with different chain lengths is helpful to improve the understanding of the immune-related interactions and provides a good theoretical basis for the design of new glycopolymer-based immune drugs.