Journal
CHEMICAL SCIENCE
Volume 3, Issue 4, Pages 996-1002Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2sc01002j
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Funding
- Fonds of the Chemical Industry
- Studienstiftung des deutschen Volkes
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The development of new non-viral transfection vectors for gene transport into cells is of current interest. A small, three-armed peptide ligand 1 is derived from the cationic dipeptide Lys-Phe with an additional anion recognition site at its N-terminus, binds to DNA with high affinity (K ca. 10(7) M-1) and efficiently delivers a GFP plasmid into cells. Compared to the cationic polymer polyethyleneimine (PEI), routinely used as a standard vector for transfection, 1 is significantly more efficient and also less cytotoxic. As DLS and AFM studies show, ligand 1 condenses DNA into tightly packed cationic aggregates which are then taken up by the cells. In contrast, the analogous divalent peptide ligand 2 of identical amino acid sequence and the highly charged divalent DNA-binder 3 (Lys-Lys-Arg) do not enable gene delivery though they also bind with high affinity (2: K ca. 10(6) M-1; 3: K ca. 10(7) M-1). All three ligands are able to transfer genetic material into cells but only the trivalent gene carrier is able to escape from the endosome due to its superior buffering capacity.
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