A Synthetic Method for Site-Specific Functionalized Polypeptides: Metal-Free, Highly Active, and Selective at Room Temperature

Functionalized polypeptides have attracted tremendous interest in recent years and found many stimulating applications owing to their tunable physicochemical characteristics including hydrophilicity and stimuli-responsive behavior. The development of new strategies to produce these polymers without metallic contaminants is crucial for their applications in high-value and sensitive domains, such as biomedical, microelectronic, food-packaging, and personal beauty care fields. Herein, a highly efficient strategy to access well-defined site-specific functionalized polypeptides is developed by combining Michael reaction with hydrogen-bonding organocatalytic ROP of NCA. A library of chain-end and chain-middle functionalized polypeptides (14 examples) with predesigned molecular weights and low polydispersities are readily prepared with this approach. Specifically, the whole synthetic process is metal-free, fulfilling high activity and selectivity at room temperature.

Automated summary

Functionalized polypeptides have gained significant interest in various fields due to their tunable physicochemical characteristics, and developing strategies to produce them without metallic contaminants is crucial for applications in high-value and sensitive domains. A highly efficient strategy combining Michael reaction with hydrogen-bonding organocatalytic ROP has been developed to access site-specific functionalized polypeptides with predesigned molecular weights and low polydispersities. This metal-free synthetic process offers high activity and selectivity at room temperature for preparing a library of chain-end and chain-middle functionalized polypeptides.