Heparan Sulfate Mimetics Differentially Affect Homologous Chemokines and Attenuate Cancer Development

Achieving
selective inhibition of chemokine activity by structurally
well-defined heparan sulfate (HS) or HS mimetic molecules can provide
important insights into their roles in individual physiological and
pathological cellular processes. Here, we report a novel tailor-made
HS mimetic, which furnishes an exclusive iduronic acid (IdoA) scaffold
with different sulfation patterns and oligosaccharide chain lengths
as potential ligands to target chemokines. Notably, highly sulfated-IdoA
tetrasaccharide (I-45) exhibited strong binding to CCL2
chemokine thereby blocking CCL2/CCR2-mediated in vitro cancer cell invasion and metastasis. Taken together, IdoA-based
HS mimetics offer an alternative HS substrate to generate selective
and efficient inhibitors for chemokines and pave the way to a wide
range of new therapeutic applications in cancer biology and immunology.