A chiral
cyclic α,α-disubstituted α-amino acid,
(S)-(−)-cucurbitine, which has a pyrrolidine
ring with a chiral center at the α-position, was synthesized,
and its homopeptides were prepared. (S)-(−)-Cucurbitine
homopeptides with a Boc-protecting group formed helical structures
with slight control of the helical screw sense to the left-handed
form. The state of the pyrrolidine ring in (S)-(−)-cucurbitine
was important for the control of the helical structures and helical
screw sense of its homopeptides.
Prolonging the duration of protein expression from mRNA is a major challenge in the development of mRNA nanomedicines. mRNA complexed with helix foldamer oligopeptides consisting of arginine and α-aminoisobutyric acids...
Amphipathic peptides composed of cationic amino acids and hydrophobic amino acids have cellpenetrating ability and are often used as a delivery tool for membrane-impermeable compounds. Small interfering RNA (siRNAs) are one of the delivery targets for such cell-penetrating peptides (CPPs). Cationic CPPs can associate with anionic siRNAs by electrostatic interactions resulting in the formation of nano-sized complexes, which can deliver siRNAs intracellularly. CPPs containing unnatural amino acids offer promising tools to siRNA delivery. However, the detailed structure-activity relationship in siRNA delivery has been rarely studied. In the current study, we designed peptides containing dipropylglycine (Dpg) and explored the cellular uptake and cytotoxicity of peptide/siRNA complexes. The amphipathic structure of the peptides played a key role in complexation with siRNAs and intracellular siRNA delivery. In the amphipathic peptides, cellular uptake of siRNA increased with increasing peptide length, but cytotoxicity was reduced. A peptide containing four Dpg exhibited an effective gene-silencing effect with small amounts of peptides without cytotoxicity in medium containing serum. These findings will be helpful for the design of novel CPPs for siRNA delivery.
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