Figure 3.

Different ways for therapeutic intervention in protein–GAG signalling. sequence-specific GAG – Oligo within a proteoglycan side chain; antibody. (A) Antibody approach. The binding of a protein to a (specific) GAG chain can be prevented by an antibody to either the (proteo-)glycan or the protein interaction partner. (A.1) The GAG-bound protein may not be targetable by the antibody raised against the soluble protein as structural rearrangements of the protein upon GAG binding as well as the change of overall/surface charge influence/destroy the antibody binding epitope. (B) Glycan- or glycan mimetic-based approach. The protein–GAG interaction can be antagonized by the addition of the synthesized protein-specific GAG sequence (or a mimetic thereof) which displaces the target protein from the natural GAG ligand. (C) Protein-based approach. The protein–GAG interaction can be antagonized by the addition of a mutant form of the target protein which exhibits higher affinity towards the natural GAG ligand and thereby displaces the wild-type target protein from the GAG chain. GAG, glycosaminoglycan.