Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses
Figure 8
Interactions observed during a 4.8 ns molecular dynamics simulation of the partially glycosylated dendrimer – human MD-2 complex.
Red – number of contacts of 1.3 Å between the dendrimer's surface glucosamine molecules and human MD-2. Blue – number of contacts of 1.3 Å between the partially glycosylated dendrimer (taking the molecule in its entirety) and human MD-2. Green – number of intermolecular hydrogen bond contacts between the partially glycosylated dendrimer (taking the molecule in its entirety) and human MD-2. Taken together, these results show that the affinity of the partially glycosylated dendrimer for human MD-2 involved both the dendrimer's surface glucosamine molecules and several of its peripheral carboxylic acid branches. Notably, these hydrogen bond interactions increased with time. This enabled the partially glycosylated dendrimer to block the entrance to human MD-2's hydrophobic pocket and thereby prevent access of the lipid chains of LPS.