Chondroitin Sulfate Tetrasaccharides : Synthesis, Three-Dimensional Structure and Interaction with Midkine

Deciphering the molecular basis underlying the interactions between growth factor and glycosaminoglycans still remains a challenging problem from the standpoint of structural glycobioloby. The article is a masterpiece where carbohydrate synthesis and a wide range of characterization methods work at unison to characterize the detailed binding between a neuro and tumourigenesis cytokine (midkine) and a well characterized fragment of a synthetic chondroitin sulfate-like tetrasaccharide.

The results given from MD simulations, STD NMR spectroscopy and computational docking simulation converge towards a picture where the tetrasaccharide binds to the internal region of the midkine formed by the two folded domains and the hinge. Whereas this mode of binding is in a good agreement with that previously proposed for the interaction between midkine and fondaparinux, it remains to elucidate the influence of the length of the glycosaminoglycan in the interaction with midkine.