title: Synthesis of conformation switchable cationic polypeptides based on poly(S-propargyl-cysteine) for use as siRNA delivery.
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.
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yi
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
authors.forename: Yisi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
authors.forename: Guanliang
authors.initials: G
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
authors.forename: Danling
authors.initials: D
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China. Electronic address: hyug@gzhmu.edu.cn.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China. Electronic address: gzhygd@gzhmu.edu.cn.
authors.forename: Guodong
authors.initials: G
authors.lastname: Ye
mesh_terms: D060326:Chemistry Techniques, Synthetic; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry*; D000072757:Protein Conformation, beta-Strand; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics; D013696:Temperature; D014162:Transfection
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D034741:RNA, Small Interfering
keywords: Cationic polypeptides; Conformation; siRNA delivery