Nonionic Water-Soluble Oligo(ethylene glycol)-Modified Polypeptides with a β-Sheet Conformation

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Protein Secondary Structure

Background:

• Polypeptide secondary structures (α-helix, β-sheet) dictate function, but water-soluble β-sheet structures are difficult to achieve.
• Controlling polypeptide secondary structure is crucial for developing advanced biomaterials and functional polymers.

Purpose of the Study:

• To synthesize and characterize oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EG-K-NCA) and their corresponding polymers (EG-K).
• To investigate the influence of ethylene glycol (EG) length and polymer degree of polymerization (DP) on the secondary structure of EG-K polymers.
• To explore the potential of these polymers in forming hydrogels and achieving specific conformations, particularly the challenging β-sheet.

Main Methods:

• Synthesis of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EG^mK-NCA) with varying EG lengths (m=1-3).
• Polymerization of EG^mK-NCA to yield EG^mK polymers with controlled degree of polymerization (n).
• Characterization of polymer secondary structures (β-sheet, α-helix) using spectroscopic techniques and assessment of water solubility and hydrogel formation.

Main Results:

• EG^mK polymer secondary structure is tunable by both EG length (m) and DP (n).
• EG²K polymers adopt a β-sheet conformation with good water solubility at appropriate DP, forming hydrogels at 1 wt%.
• EG¹K polymers show tunable secondary structures (β-sheet or α-helix) based on DP, while EG³K polymers form stable α-helices independent of DP.

Conclusions:

• The urethane connecting unit plays a significant role in regulating polypeptide secondary structure, an unexpected finding compared to previous studies.
• This work provides a versatile platform for designing polypeptides with controlled secondary structures, including rare water-soluble β-sheets.
• The developed EG-K polymers demonstrate potential for applications in hydrogel formation and advanced biomaterials.