Kato Takuma, Oba Makoto, Nishida Koyo, 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. 2018 Apr 9;4(4):1368-1376. doi: 10.1021/acsbiomaterials.8b00180. Epub 2018 Mar 14.
In the delivery of cell-impermeable molecules, cell-penetrating peptides (CPPs) have been attracting increasing attention as intracellular delivery tools. In the present study, we designed four types of cyclic α,α-disubstituted α-amino acids (dAAs) with basic functional groups on their five-membered rings and different chiralities at the α-position and introduced them into arginine (Arg)-rich peptides. The evaluation of cell-penetrating abilities indicated that these peptides exhibited better cell permeabilities than an Arg nonapeptide. Furthermore, peptides containing dAAs delivered plasmid DNA (pDNA) better than a commercially available transfection reagent with a longer incubation time. These results demonstrate that the introduction of cyclic dAAs with basic functional groups into Arg-rich peptides is an effective strategy for the design of CPPs as a pDNA delivery tool.
在递送细胞不可渗透分子时，细胞穿透肽（CPPs）作为细胞内递送工具正受到越来越多的关注。在本研究中，我们设计了四种类型的环状α,α-二取代α-氨基酸（dAAs），其五元环上带有碱性官能团，且α位具有不同的手性，并将它们引入富含精氨酸（Arg）的肽中。细胞穿透能力评估表明，这些肽比精氨酸九肽表现出更好的细胞通透性。此外，含有dAAs的肽在较长孵育时间下递送质粒DNA（pDNA）的效果优于市售转染试剂。这些结果表明，将带有碱性官能团的环状dAAs引入富含Arg的肽中是设计作为pDNA递送工具的CPPs的有效策略。
