Kadota Koji, Kohata Ai, Sando Shinsuke, Morimoto Jumpei, Aikawa Kohsuke, Okazoe Takashi
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo 2-11-16 Yayoi, Bunkyo-ku Tokyo 113-0032 Japan.
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku Tokyo 113-8656 Japan
RSC Adv. 2025 Mar 17;15(11):8189-8194. doi: 10.1039/d5ra00304k.
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.
评估了全氟烷基（R）和烷基（R）基团对短肽细胞摄取作用的差异。建立了一种简便的合成方法来制备侧链带有R和R基团的Fmoc保护氨基酸。使用固相肽合成法成功地将合成的Fmoc保护氨基酸掺入肽中。与具有相同侧链长度R基团的肽相比，具有R基团的肽表现出更高的细胞摄取效率。有趣的是，尽管细胞摄取效率相似，但AF-R-三肽（R = CF）的细胞毒性低于AF-R-三肽（R = CH）。对肽与脂质体膜结合亲和力的评估表明，与R基团相比，R基团更高的疏脂性导致了在具有R基团的肽中观察到较低的细胞毒性。这些发现表明，将R基团引入肽中对于开发具有提高摄取效率和低细胞毒性的药物递送载体具有相当大的潜力。
