Chondroitin sulfate (CS) and
dermatan sulfate (DS) interact with various extracellular molecules such as
growth factors,
cytokines/
chemokines,
neurotrophic factors, morphogens, and
viral proteins, thereby playing roles in a variety of biological processes including cell adhesion, proliferation, tissue morphogenesis, neurite outgrowth,
infections, and
inflammation/leukocyte trafficking. CS/DS are modified with
sulfate groups at C-2 of
uronic acid residues as well as C-4 and/or C-6 of
N-acetyl-D-galactosamine residues, yielding enormous structural diversity, which enables the binding with numerous
proteins. We have demonstrated that highly sulfated CS-E from squid cartilage, for example, interacts with
heparin-
binding proteins including
midkine,
pleiotrophin, and
fibroblast growth factors expressed in brain with high affinity (Kd values in the nM range). Here, we analyzed the binding of CS and DS, which have a relatively low degree of sulfation and have been widely used as a nutraceutical and a
drug for
osteoarthritis etc., with a number of
heparin-binding
neurotrophic factors/
cytokines using surface plasmon resonance (SPR) and structurally characterized the CS/DS chains. SPR showed that relatively low sulfated CS-A, DS, and CS-C also bound with significant affinity to
midkine,
pleiotrophin,
hepatocyte growth factor, monokine-induced by
interferon-γ, and stromal cell derived factor-1β, although the binding was less intense than that with highly sulfated CS-D and CS-E. These findings suggest that even low sulfated CS and/or DS chains may contain binding domains, which include fine
sugar sequences with specific sulfation patterns, and that
sugar sequences, conformations and electrostatic potential are more important than the simple degree of sulfation represented by
disaccharide composition.