Modulation of Conformational Transition of Polypeptides under Slightly Acidic Environment†

Comprehensive Summary Controlling the conformational transition of polypeptides under slightly acidic environment is challenging. Herein, we report a class of pH-responsive helix-to-coil conformationally transitionable polypeptides (pCTPs) by simply conjugating tertiary amine groups (TAs) to polylysine. Their conformation is highly dependent on the charge state of TAs, showing a helical structure when most TAs are deprotonated and a non-helical structure when majority of TAs are protonated. The conformational transition pH can be modulated by tuning the hydrophobicity of TAs and the incorporation of hydrophobic monomers at a pH range of 7.2 to 6.0. Such pCTP showed a vesicle-to-micelle transition when their conformation transformed from helix to coil, facilitating controlled drug release. Our study provided an approach to control the conformational transition of polypeptides under slightly acidic condition.

Automated summary

In this study, a class of pH-responsive helix-to-coil conformationally transitionable polypeptides (pCTPs) was developed by conjugating tertiary amine groups (TAs) to polylysine. The conformation of pCTPs can be controlled by the charge state of TAs and hydrophobicity, and this transition facilitates controlled drug release.