Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis

Prashant Jain; Chethan D. Shanthamurthy; Shani Leviatan Ben-Arye; Sharon Yehuda; Sharvani S. Nandikol; Hirekodathakallu V. Thulasiram; Vered Padler-Karavani; Raghavendra Kikkeri

doi:10.1039/d1cc00964h

Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis

Prashant Jain, Chethan D. Shanthamurthy, Shani Leviatan Ben-Arye, Sharon Yehuda, Sharvani S. Nandikol, Hirekodathakallu V. Thulasiram, Vered Padler-Karavani^*, Raghavendra Kikkeri

^*Corresponding author for this work

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11 Scopus citations

Abstract

We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF₁₆₅, HB-EGF, and FGF2. Notably,GlcNHAc(6-O-SO₃⁻)-IdoA(2-O-SO₃⁻) (HT-2,6S-NAc)tetrasaccharide showed strong binding with the VEGF₁₆₅growth factor.In vitrovascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF₁₆₅andHT-2,6S-NAcorHT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.

Original language	English
Pages (from-to)	3516-3519
Number of pages	4
Journal	Chemical Communications
Volume	57
Issue number	28
DOIs	https://doi.org/10.1039/d1cc00964h
State	Published - 11 Apr 2021

Funding

Funders	Funder number
Department of Biotechnology, Ministry of Science and Technology, India	BT/PR21934/NNT/28/1242/ 2017, SERB/F/9228/2019–2020, STARS/APR2019/CS/426/FS
Department of Science and Technology, Ministry of Science and Technology, India	SR/ NM/NS-1113/2016
Israel Science Foundation
Indian Institute of Science Education and Research Pune

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title = "Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis",

abstract = "We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF165, HB-EGF, and FGF2. Notably,GlcNHAc(6-O-SO3−)-IdoA(2-O-SO3−) (HT-2,6S-NAc)tetrasaccharide showed strong binding with the VEGF165growth factor.In vitrovascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF165andHT-2,6S-NAcorHT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.",

author = "Prashant Jain and Shanthamurthy, {Chethan D.} and {Leviatan Ben-Arye}, Shani and Sharon Yehuda and Nandikol, {Sharvani S.} and Thulasiram, {Hirekodathakallu V.} and Vered Padler-Karavani and Raghavendra Kikkeri",

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doi = "10.1039/d1cc00964h",

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AU - Jain, Prashant

AU - Shanthamurthy, Chethan D.

AU - Leviatan Ben-Arye, Shani

AU - Yehuda, Sharon

AU - Nandikol, Sharvani S.

AU - Thulasiram, Hirekodathakallu V.

AU - Padler-Karavani, Vered

AU - Kikkeri, Raghavendra

PY - 2021/4/11

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N2 - We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF165, HB-EGF, and FGF2. Notably,GlcNHAc(6-O-SO3−)-IdoA(2-O-SO3−) (HT-2,6S-NAc)tetrasaccharide showed strong binding with the VEGF165growth factor.In vitrovascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF165andHT-2,6S-NAcorHT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.

AB - We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF165, HB-EGF, and FGF2. Notably,GlcNHAc(6-O-SO3−)-IdoA(2-O-SO3−) (HT-2,6S-NAc)tetrasaccharide showed strong binding with the VEGF165growth factor.In vitrovascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF165andHT-2,6S-NAcorHT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.

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Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis

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