Heparan Sulfate Mimetics Differentially Affect Homologous Chemokines and Attenuate Cancer Development
Chethan D. Shanthamurthy, Shani Leviatan Ben‐Arye, Nanjundaswamy Vijendra Kumar, Sharon Yehuda, Ron Amon, Robert J. Woods, Vered Padler‐Karavani, Raghavendra Kikkeri
Abstract
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.