pH-responsive bioactive glycopolypeptides with enhanced helicity and solubility in aqueous solution

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Bioconjugation Chemistry

Background:

• Copolypeptides offer tunable properties for advanced applications.
• Introducing carbohydrate moieties can modulate polypeptide behavior.
• Controlled synthesis of functional polypeptides remains a key challenge.

Purpose of the Study:

• To synthesize novel glucocopolypeptides with controlled structures.
• To investigate the impact of glucose conjugation on polypeptide conformation and stability.
• To explore the binding interactions of these glucocopolypeptides with lectins.

Main Methods:

• Ring-opening polymerization for polypeptide backbone synthesis.
• Thiol-ene/yne photochemistry for mild glucose conjugation.
• Circular dichroism spectroscopy to analyze secondary structure.
• Turbidity assays for lectin binding studies.

Main Results:

• Successfully synthesized copolypeptides of L-glutamate and glucosylated L-/DL-allyl- or DL-propargylglycine.
• Glucosylated and non-glucosylated polypeptides displayed pH-dependent conformational changes (random-coil to α-helical).
• Glucocopolypeptides demonstrated enhanced helical stability and solubility at acidic pH (down to 3.5).
• Selective binding of glucocopolypeptides to concanavalin A was confirmed.

Conclusions:

• Mild, aqueous synthesis enabled efficient glucose introduction into polypeptides.
• Glucose conjugation significantly improved helical stability and solubility.
• The developed glucocopolypeptides show specific interactions with plant lectins, suggesting potential in biosensing or drug delivery.