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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3367-3380
Number of pages14
JournalJournal of Medicinal Chemistry
Volume64
Issue number6
DOIs
StatePublished - 25 Mar 2021

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