Salt- and pH-Triggered Helix–Coil Transition of Ionic Polypeptides under Physiology Conditions

Controlling the helix–coil transition of polypeptides under physiological conditions is an attractive way toward smart functional materials. Here, we report the synthesis of a series of tertiary amine-functionalized ethylene glycol (EGx)-linked polypeptide electrolytes with their secondary structures tunable under physiological conditions. The resultant polymers, denoted as P(EGxDMA-Glu) (x = 1, 2, and 3), show excellent aqueous solubility (>20 mg/mL) regardless of their charge states. Unlike poly-l-lysine that can form a helix only at pH above 10, P(EGxDMA-Glu) undergo a pH-dependent helix–coil switch with their transition points within the physiological range (pH ∼5.3–6.5). Meanwhile, P(EGxDMA-Glu) exhibit an unusual salt-induced helical conformation presumably owing to the unique properties of EGx linkers. Together, the current work highlights the importance of fine-tuning the linker chemistry in achieving conformation-switchable polypeptides and represents a facile approach toward stimuli-responsive biopolymers for advanced biological applications.