What does this research mean for the field?

Aminoglycoside-derived heparan sulfate mimetics, specifically those with targeted N-acetylation and 6-O-sulfation, can serve as synthetically accessible platforms to potently and selectively disrupt growth factor binding and inhibit FGF2-induced cell proliferation. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To synthesize structurally defined, non-native heparan sulfate mimetics to systematically evaluate structure–activity relationships governing growth factor recognition and signaling modulation.

August 22, 2026Journal of Medicinal ChemistryOpen Access

Synthetic Heparan Sulfate-like Oligosaccharides as Tools to Decipher Growth Factor Recognition

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Authors

JWJoseph Wakpal KSKartikey Singh MHMichael Hotor

Discussion

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Overview

In vitro study demonstrates synthetic heparan sulfate mimetics disrupt growth factor binding and inhibit proliferation in fibroblast cells, highlighting a novel platform to target signaling.

Key Points

To synthesize structurally defined, non-native heparan sulfate mimetics to systematically evaluate structure–activity relationships governing growth factor recognition and signaling modulation.
Synthesized a diverse library of 46 aminoglycoside-derived non-native heparan sulfate (HS) mimetics with varying functional groups.
Conducted structure–activity relationship (SAR) profiling to measure competitive inhibition of heparin binding to FGF2, FGFR1, and VEGF165.
Assessed the biological activity, selectivity, and cytotoxicity of candidate compound 8 in FGF2-induced NIH3T3 fibroblast proliferation assays.
SAR analysis identified N-acetylation and 6-O-sulfation as critical structural determinants for modulating interactions with FGF2 and VEGF165.
Compound 8 competitively disrupted heparin binding to FGF2 (IC50 = 0.23 μM), FGFR1 (IC50 = 0.17 μM), and VEGF165 (IC50 = 0.66 μM), demonstrating >140-fold FGF2/FGF4 selectivity and higher potency than native HS pentasaccharide fondaparinux.
Compound 8 selectively decreased FGF2-induced proliferation in NIH3T3 fibroblasts in a dose-dependent manner without measurable cytotoxicity.

Cite This Study

Wakpal et al. (2026) studied this question.

synapsesocial.com/papers/6a89600eca7ade938187f167 https://doi.org/10.1021/acs.jmedchem.6c00760

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August 22, 2026Journal of Medicinal ChemistryOpen Access

Synthetic Heparan Sulfate-like Oligosaccharides as Tools to Decipher Growth Factor Recognition

View Full Paper

Ask AI

Bookmark

Authors

JWJoseph Wakpal KSKartikey Singh MHMichael Hotor

Discussion

Member takes

Overview

In vitro study demonstrates synthetic heparan sulfate mimetics disrupt growth factor binding and inhibit proliferation in fibroblast cells, highlighting a novel platform to target signaling.

Key Points

To synthesize structurally defined, non-native heparan sulfate mimetics to systematically evaluate structure–activity relationships governing growth factor recognition and signaling modulation.
Synthesized a diverse library of 46 aminoglycoside-derived non-native heparan sulfate (HS) mimetics with varying functional groups.
Conducted structure–activity relationship (SAR) profiling to measure competitive inhibition of heparin binding to FGF2, FGFR1, and VEGF165.
Assessed the biological activity, selectivity, and cytotoxicity of candidate compound 8 in FGF2-induced NIH3T3 fibroblast proliferation assays.
SAR analysis identified N-acetylation and 6-O-sulfation as critical structural determinants for modulating interactions with FGF2 and VEGF165.
Compound 8 competitively disrupted heparin binding to FGF2 (IC50 = 0.23 μM), FGFR1 (IC50 = 0.17 μM), and VEGF165 (IC50 = 0.66 μM), demonstrating >140-fold FGF2/FGF4 selectivity and higher potency than native HS pentasaccharide fondaparinux.
Compound 8 selectively decreased FGF2-induced proliferation in NIH3T3 fibroblasts in a dose-dependent manner without measurable cytotoxicity.

Cite This Study

Wakpal et al. (2026) studied this question.

synapsesocial.com/papers/6a89600eca7ade938187f167 https://doi.org/10.1021/acs.jmedchem.6c00760

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