Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

International Journal of Molecular Sciences

卷:22

Emilia Sikorska¹  Agnieszka Piwkowska¹  Magdalena Wysocka¹  Aleksandra Gnatek¹  Adam Lesner¹  Anita Romanowska¹  Igor Konieczny²  Katarzyna Bury²  Katarzyna Węgrzyn² 

[1] Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland;

[2] Intercollegiate Faculty of Biotechnology, University of Gdansk Abrahama 58, 80-308 Gdansk, Poland;

关键词: polymers;    peptidomimetics;    AFM;    transfection;    molecular modelling;   

DOI  :  10.3390/ijms22052571

来源: DOAJ

【 摘 要 】

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 µM, 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.

【 授权许可】

Unknown