Oba Makoto, Ito Yurika, Umeno Tomohiro, Kato Takuma, Tanaka Masakazu
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Osaka University of Pharmaceutical Sciences, 40-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):5660-5668. doi: 10.1021/acsbiomaterials.8b01451. Epub 2019 Apr 22.
Arginine (Arg)-rich cell-penetrating peptides (CPPs) are promising tools for plasmid DNA (pDNA) delivery. α-Aminoisobutyric acid (Aib) is known to stabilize peptide helical secondary structures and has been used as a building block for foldamers. In the current study, we prepared Aib CPP foldamers, (Arg-Arg-Aib) ( = 1-6) and examined their pDNA transfection abilities. Transfection efficiencies of peptide/pDNA complexes are dependent on peptide chain length, with longer peptides ( ≥ 4) exhibiting better transfection abilities than an Arg nonapeptide. Furthermore, Aib CPP foldamers achieve prolonged transfection abilities compared with commercially available transfection reagents, which is probably because of the high resistance of the peptides to enzymatic degradation, thereby protecting the encapsulated pDNA for a long period. The obtained results demonstrated promising features of Aib CPP foldamers as pDNA delivery carriers.
富含精氨酸（Arg）的细胞穿透肽（CPPs）是用于质粒DNA（pDNA）递送的有前景的工具。已知α-氨基异丁酸（Aib）可稳定肽的螺旋二级结构，并已用作折叠体的构建模块。在本研究中，我们制备了Aib CPP折叠体（Arg-Arg-Aib）（n = 1-6）并检测了它们的pDNA转染能力。肽/pDNA复合物的转染效率取决于肽链长度，较长的肽（n≥4）比较短的精氨酸九肽表现出更好的转染能力。此外，与市售转染试剂相比，Aib CPP折叠体具有更长的转染能力，这可能是因为这些肽对酶促降解具有高度抗性，从而长期保护包裹的pDNA。所得结果证明了Aib CPP折叠体作为pDNA递送载体的良好特性。
