Comparison of the effects of perfluoroalkyl and alkyl groups on cellular uptake in short peptides.

The differences in the effects of perfluoroalkyl (R) and alkyl (R) groups on the cellular uptake of short peptides were evaluated. A facile synthetic method was established to produce Fmoc-protected amino acids bearing R and R groups on their side chains. The synthesized Fmoc-protected amino acids were successfully incorporated into peptides using solid-phase peptide synthesis. Peptides with an R group exhibited higher cellular uptake efficiency compared to peptides with an R group of the same side-chain length. Intriguingly, the cytotoxicity of the AF-R-tripeptide (R = CF) was lower than that of the AF-R-tripeptide (R = CH), despite similar cellular uptake efficiencies. An evaluation of the binding affinity of the peptides to liposome membranes suggested that the higher lipophobicity of the R group, compared to the R group, contributed to the lower cytotoxicity observed in the peptide with the R group. These findings indicate that the introduction of an R group into peptides has considerable potential for developing drug-delivery carriers with enhanced uptake efficiency and low cytotoxicity.