Hyaluronan (HA)-inspired glycopolymers as molecular tools for studying HA functions

Area of Science:

• Glycochemistry
• Polymer Science
• Biochemistry

Background:

• Hyaluronic acid (HA) is a crucial glycosaminoglycan with diverse biological roles.
• Its precise mechanisms of action, particularly receptor interactions, remain incompletely understood.
• Glycopolymers offer a synthetic route to study HA structure-function relationships.

Purpose of the Study:

• To synthesize and characterize hyaluronic acid (HA) glycopolymers.
• To investigate the binding interactions of these glycopolymers with known HA-binding proteins and lectins.
• To explore the potential of HA glycopolymers as inhibitors of hyaluronidase (HAase).

Main Methods:

• Synthesis of HA glycopolymers using reversible addition-fragmentation chain transfer (RAFT) polymerization and copper alkyne-azide cycloaddition.
• Surface plasmon resonance (SPR) to assess binding affinities to HA-binding proteins (CD44, hyaluronidase) and lectins (Dectin-1, DEC-205).
• Evaluation of HA glycopolymers' inhibitory effect on hyaluronidase activity.

Main Results:

• Successful synthesis of homo, statistical, and alternating HA glycopolymers with pendant N-acetyl glucosamine (GlcNAc) and glucuronic acid (GlcA) monosaccharides.
• Identification of structure-binding relationships between HA monosaccharides and receptors.
• Discovery of novel HA binders, including Dectin-1 and DEC-205 lectins.
• Demonstration of inhibitory effects of GlcNAc- and GlcA-based glycopolymers on hyaluronidase activity.

Conclusions:

• HA glycopolymers provide a valuable tool for elucidating HA-receptor interactions.
• These synthetic glycopolymers reveal novel binding partners for HA.
• GlcNAc- and GlcA-based glycopolymers show promise as potential hyaluronidase inhibitors.