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Updated: Sep 13, 2025
12:24
Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
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Unravelling structure-function interactions between fluorinated heparan sulfate mimetics and signaling proteins
Virendrasinh Mahida1, Rakesh Raigawali1, Paula González2
1Department of Chemistry, Indian Institute of Science Education and Research Pune 411008 India rkikkeri@iiserpune.ac.in.
RSC Chemical Biology
|August 4, 2025
Summary
Fluorinated carbohydrates offer new ways to study protein binding and develop drugs. Synthesized heparan sulfate mimetics with fluorine showed retained binding properties, paving the way for new therapeutics.
Area of Science:
- Glycobiology
- Medicinal Chemistry
- Carbohydrate Chemistry
Background:
- Fluorinated carbohydrates are valuable tools in glycobiology.
- They help elucidate hydroxyl group roles in protein binding and drug discovery.
Purpose of the Study:
- To synthesize heparan sulfate (HS) mimetics with fluorine at the C3 position of the glucuronic acid residue.
- To modulate structure-function relationships and assess binding properties.
Main Methods:
- Divergent synthesis strategy.
- 19F-NMR spectroscopy, 3JHH coupling, and NOE data analysis.
- Glycan microarray and SPR binding studies.
Main Results:
- Seven HS mimetics with C3-fluorinated glucuronic acid were synthesized.
- Fluorine substitution confirmed sensitivity to sulfation patterns and retained glucuronic acid conformation.
- HS mimetics retained binding of N-acetylated HS sequences for growth factors and chemokines.
- Specific fluorinated mimetics showed binding comparable to highly N-sulfated native HS ligands.
Conclusions:
- Hydroxyl-to-fluorine substitution in HS mimetics is a viable strategy to modulate structure-function relationships.
- These findings support the development of novel therapeutic agents targeting morphogens and cell signaling pathways.
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