Glycopolymers Prepared by Alternating Ring-Opening Metathesis Polymerization Provide Access to Distinct, Multivalent...

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Molecular Biology

Background:

• Ligand-receptor interactions are crucial for biological processes, often requiring multivalent binding for enhanced affinity.
• Synthetic multivalent probes with controlled ligand display are essential for investigating these interactions.
• Precise control over ligand spacing and polymer backbone properties is needed for tailored biological probes.

Purpose of the Study:

• To synthesize and characterize novel glycopolymers with precise ligand spacing and tunable backbone properties.
• To investigate the solution conformations of these glycopolymers using small-angle X-ray scattering (SAXS).
• To evaluate the biological activity of these glycopolymers in a sperm acrosomal exocytosis (AE) assay.

Main Methods:

• Alternating ring-opening metathesis polymerization was used to synthesize glycopolymers from bicyclo[4.2.0]oct-6-ene-7-carboxamide and either 4,7-dihydro-1,3-dioxepin or cyclohexene.
• Small-angle X-ray scattering (SAXS) was employed to determine polymer conformations in aqueous solution.
• A biological assay was conducted to assess the ability of the glycopolymers to activate acrosomal exocytosis in mouse sperm.

Main Results:

• The synthesized [4.2.0] glycopolymers exhibited precise ligand spacing and offered either hydrophobic or acetal-functionalized backbones.
• [4.2.0]-dioxepin glycopolymers adopted flexible, rod-like structures, while [4.2.0]-cyclohexene glycopolymers formed compact, globular structures in solution.
• [4.2.0]-cyclohexene glycopolymers successfully induced acrosomal exocytosis in mouse sperm, whereas [4.2.0]-dioxepin glycopolymers did not.

Conclusions:

• The study presents two distinct glycopolymer structures with controlled conformations and low cytotoxicity, suitable for biological applications.
• The distinct structural conformations of the glycopolymers lead to differential biological responses, highlighting their potential as tailored probes.
• These novel glycopolymers provide versatile tools for investigating ligand-receptor interactions and modulating specific biological processes like acrosomal exocytosis.