Guanidine-rich helical polypeptides bearing hydrophobic amino acid pendants for efficient gene delivery
| Autor: | Haoyu Tang, Lichen Yin, Chenglong Ge, Ziyin Zhao, Ziyuan Song, Zhimin Zhang, Zikun Yu, Jing Yan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
biology Chemistry Biomedical Engineering Gene Transfer Techniques Transfection Genetic Therapy Gene delivery biology.organism_classification Combinatorial chemistry Amino acid HeLa chemistry.chemical_compound In vivo Animals Humans Polyethyleneimine General Materials Science Amino Acids Guanidine Cytotoxicity Peptides DNA |
| Zdroj: | Biomaterials science. 9(7) |
| ISSN: | 2047-4849 |
| Popis: | Non-viral gene delivery vectors with high transfection efficiency both in vitro and in vivo and low cytotoxicity are highly desirable for clinical applications. Herein, a series of guanidine-rich polypeptides bearing hydrophobic amino acid pendants was efficiently prepared via the 1,3-dipolar cycloaddition between azido decorated polypeptide and propargyl functionalized guanidinium and N-acetylamino acids. CD analysis indicated α-helical conformations of all resulting polypeptides in aqueous solution. The guanidine-rich polypeptide/DNA complexes showed significantly enhanced cellular internalization and high cell viability (>90%) in different mammalian cell lines (i.e., HeLa and RAW 264.7) at concentrations of the best performance. The top-performing guanidine-rich polypeptide containing 10% N-acetyl-l-valine pendants outperformed the commercial transfection reagent PEI by 400 times in vitro and 6 times in vivo. This study provides a new guidance for future molecular design of non-viral gene vectors with high delivery efficiency and low cytotoxicity. |
| Databáze: | OpenAIRE |
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