Tunable, biodegradable grafting-from glycopolypeptide bottlebrush polymers

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Glycobiology

Background:

• The cellular glycocalyx and extracellular matrix are vital natural polymer networks rich in glycoproteins and proteoglycans.
• Synthetic mimics, or glycobrushes, are crucial for biomedicine but challenging to synthesize at high densities.

Purpose of the Study:

• To develop a novel method for synthesizing glycopolypeptide brushes with high grafting and glycosylation densities.
• To create chemically and conformationally tunable glycobrushes for biomedical applications.

Main Methods:

• Employed one-pot dual-catalysis polymerization of glycan-bearing α-amino acid N-carboxyanhydrides.
• Precisely controlled backbone and sidechain lengths, grafting density, and glycan composition.
• Synthesized cholesterol-modified glycobrushes for cell surface display.

Main Results:

• Successfully prepared grafting-from glycopolypeptide brushes with tunable properties.
• Achieved grafting densities up to 100% and controlled glycan identity and density.
• Demonstrated non-toxicity, protease degradability, and successful display on live human cells.

Conclusions:

• The developed method overcomes key challenges in synthetic glycobrush preparation.
• These defined, tunable glycobrushes offer new avenues for studying glycan presentation and multivalency.
• The materials hold promise for diverse biomedical applications, including cell surface engineering.