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

The secondary structures of polypeptides, such as an α-helix and a β-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a β-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (^EGK-NCA, where m = 1-3) and the corresponding polymers ^EGK are synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of ^EGK is delicately regulated by both m and n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, ^EG2K adopts a β-sheet conformation with good water solubility at an appropriate DP and forms physically cross-linked hydrogels at a concentration as low as 1 wt %. The secondary structures of ^EG1K can be tuned by DP, exhibiting either a β-sheet or an α-helix, whereas ^EG3K appears to a adopt pure and stable α-helix with no dependence on DP. Compared to previous works reporting EG-modified lysine-derived polypeptides bearing exclusively an α-helix conformation, this work highlights the important and unexpected role of the urethane connecting unit and provides useful case studies for understanding the secondary structure of polypeptides.