期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms22052571
关键词
polymers; peptidomimetics; AFM; transfection; molecular modelling
资金
- Narodowe Centrum Nauki [UMO-2017/27/B/ST5/02061] Funding Source: Medline
Novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues were synthesized and their cell permeability, cytotoxicity, and DNA-binding ability were investigated in this study. The compounds showed efficient cell membrane penetration, dsDNA binding, and minimal cytotoxicity. The interaction with plasmid DNA and the length of the main chain of the compounds influenced the formation of unique nanostructures.
The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)(n)-O2Oc-NH2, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 mu M, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)](8)-O2Oc-NH2 and typical for large proteins.
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