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 (EGmK-NCA, where m= 1–3) and the corresponding polymers EGmKnare synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of EGmKnis delicately regulated by both mand n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, EG2Knadopts 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 EG1Kncan be tuned by DP, exhibiting either a β-sheet or an α-helix, whereas EG3Knappears 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.