Glycosaminoglycan Mimetic Precision Glycomacromolecules with Sequence-Defined Sulfation and Rigidity Patterns

Area of Science:

• Carbohydrate Chemistry
• Glycoscience
• Medicinal Chemistry

Background:

• Sulfated glycosaminoglycans (sGAGs), like heparan sulfate (HS), are crucial in biological processes and are explored as antiviral agents.
• The biological function of sGAGs is influenced by their complex sulfation patterns, affecting flexibility and conformation.
• Current synthetic methods struggle to replicate the distinct sulfation features of sGAGs in mimetics.

Purpose of the Study:

• To develop synthetic methods for creating sulfated glycomacromolecules with defined sulfation patterns.
• To synthesize sGAG mimetics, including globally sulfated glycooligomers, sequence-defined sulfated glycooligomers, and hybrid structures.
• To evaluate the anticoagulant properties of the synthesized sGAG mimetics.

Main Methods:

• Solid-phase synthesis of sulfated glycomacromolecules.
• Utilized a photocleavable linker to preserve sensitive sulfate groups during synthesis and cleavage.
• Chemical sulfation and purification of the target molecules.

Main Results:

• Successfully synthesized three groups of sulfated glycomacromolecules with high purity and sulfation degrees.
• Demonstrated the versatility of the solid-phase methodology for creating tailor-made sGAG mimetics.
• Synthesized compounds exhibited anticoagulant activity comparable to natural HS.

Conclusions:

• The developed solid-phase synthesis is effective for producing diverse sulfated glycomacromolecules and sGAG mimetics.
• Tailor-made sGAG mimetics can be prepared with precise control over sulfation patterns.
• The synthesized compounds hold potential for applications requiring HS-like biological activity.