Arginine (Arg)-rich peptides
exhibit an effective cell-penetrating ability and deliver membrane-impermeable
compounds into cells. Here, three types
of Arg-rich peptides, R9 containing nine Arg residues, (RRG)3 containing six
Arg and three glycine (Gly) residues, and (RRX)3 containing six Arg and three a-aminoisobutyric acid (Aib)
residues, were evaluated for their plasmid DNA (pDNA) delivery and
cell-penetrating ability. The
transfection efficiency of R9/pDNA complexes was much higher than those of
(RRG)3 and (RRX)3/pDNA complexes, which was derived from the enhanced cellular
uptake of R9/pDNA complexes. The
replacement of three Arg residues with neutral amino acids Gly and hydrophobic
amino acids Aib drastically changed their cell-penetrating ability and
physicochemical properties of peptide/pDNA complexes, resulting in the markedly
reduced transfection efficiency.
Comparison of R9 peptide administration forms between peptide alone and
peptide/pDNA complex revealed that R9 peptides were uptaken much more efficient
for complex than peptide alone but through same internalization mechanism. The results of the present study will
contribute to the design of novel Arg-rich cell-penetrating peptides for pDNA
delivery.