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.
Chembiochem. 2023 Nov 2;24(21):e202300374. doi: 10.1002/cbic.202300374. Epub 2023 Jul 26.
With an increasing demand for macromolecular biotherapeutics, the issue of their poor cell-penetrating abilities requires viable and relevant solutions. Herein, we report tripeptides bearing an amino acid with a perfluoroalkyl (R ) group adjacent to the α-carbon. R -containing tripeptides were synthesized and evaluated for their ability to transport a conjugated hydrophilic dye (Alexa Fluor 647) into the cells. R -containing tripeptides with the fluorophore showed high cellular uptake efficiency and none of them were cytotoxic. Interestingly, we demonstrated that the absolute configuration of perfluoroalkylated amino acids (R -AAs) affects not only nanoparticle formation but also the cell permeability of the tripeptides. These novel R -containing tripeptides are potentially useful as short and noncationic cell-penetrating peptides (CPPs).
随着对大分子生物治疗药物需求的增加，其细胞穿透能力差的问题需要可行和相关的解决方案。在此，我们报告了在α-碳上邻接具有全氟烷基（R ）基团的氨基酸的三肽。合成了含 R 的三肽，并评估了它们将共轭亲水性染料（Alexa Fluor 647）运输到细胞内的能力。带荧光团的含 R 的三肽具有很高的细胞摄取效率，而且它们都没有细胞毒性。有趣的是，我们证明了全氟烷基化氨基酸（R -AA）的绝对构型不仅影响纳米颗粒的形成，还影响三肽的细胞通透性。这些新型的含 R 的三肽作为短的非阳离子细胞穿透肽（CPP）具有潜在的用途。
