Synthesis of conformation switchable cationic polypeptides based on poly(S-propargyl-cysteine) for use as siRNA delivery

July 28, 2017

Title

Synthesis of conformation switchable cationic polypeptides based on poly(S-propargyl-cysteine) for use as siRNA delivery

Author

Ling Yi, Yisi Wang, Guanliang Lin, Danling Lin, Wenliang Chen, Yugang Huang, Guodong Ye

Year

2017

Journal

International Journal of Biological Macromolecules

Abstract

Ring-opening polymerization of S-propargyl-cysteine-N-carboxyanhydride has been used to synthesize conformation switchable poly(S-propargyl-cysteine) starting with l-cysteine, dl- and d-cysteine. Then cationic polypeptides with different backbone chirality are obtained by nearly 100% side-chain grafting of cysteamine via thiol-yne click chemistry. The cationic polypeptides containing mixed conformations of β-sheets, β-turns and random coils are stable against pH, salt and temperature variations. The cationic polypeptides can condense siRNA at a low polypeptide/siRNA weight ratio to form nanoparticles with size depending on the backbone chirality. The cationic polypeptides derived from poly(S-propargyl-l or d-cysteine) are non-cytotoxic to HeLa and HepG2 cells, but interrupting the backbone chirality enhances the cytotoxicity sharply. The cationic polypeptides used for siRNA delivery show good transfection efficiency, but cell internalization process depends on the backbone chirality. The cationic polypeptide derived from the poly(S-propargyl-l-cysteine) is an appropriate siRNA vector with advantages of non-cytotoxicity and high transfection efficiency.

Instrument

J-810

Keywords

Circular dichroism, Secondary structure, Stereochemistry, Thermal stability, Chemical stability, Biochemistry