TY - JOUR
T1 - Heparan Sulfate Mimetics Differentially Affect Homologous Chemokines and Attenuate Cancer Development
AU - Shanthamurthy, Chethan D.
AU - Leviatan Ben-Arye, Shani
AU - Kumar, Nanjundaswamy Vijendra
AU - Yehuda, Sharon
AU - Amon, Ron
AU - Woods, Robert J.
AU - Padler-Karavani, Vered
AU - Kikkeri, Raghavendra
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/3/25
Y1 - 2021/3/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103462045&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.0c01800
DO - 10.1021/acs.jmedchem.0c01800
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C2 - 33683903
AN - SCOPUS:85103462045
SN - 0022-2623
VL - 64
SP - 3367
EP - 3380
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
ER -
