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Oxidation-Responsive OEGylated Poly-L-cysteine and Solution Properties Studies

Biomacromolecules 2014, 15, 1055-1061.

Xiaohui Fu, Yinan Ma, Yong Shen, Wenxin Fu, and Zhibo Li*. 

The oxidation-responsive behaviors of OEGylated poly-L-cysteine homopolypeptides, that is, poly(L-EGxMA-C)n, were investigated. These poly-L-cysteine derivatives adopted mixed conformation in water, in which the β-sheet accounted for a significant proportion. Upon oxidation, the thioethers in polypeptide side chains were converted to polar sulfone groups, which triggered the secondary structure ransition from β-sheet preferred conformation to random coil. Accordingly, the increase of side-chain polarity together with conformation changes increased samples' water solubility and cloud point temperature. Using mPEG45-NH2 as macroinitiator, we synthesized PEG45-b-poly(L-EG2MA-C)22 diblock copolymer via ring-opening polymerization (ROP) of L-EG2MA-C N-carboxyanhydride (NCA). The PEG45-b-poly(L-EG2MA-C)22 was able to self-assemble into spherical micelles in aqueous solution, and the micelles could undergo an oxidation-triggered disassembly due to the oxidation-responsive thioethers. Such a new class of oxidation-responsive polypeptides might provide a promising platform to construct inflammation targeting drug delivery systems.

Responsive mechanism of OEGylated poly-L-cysteine.