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.

中文翻译：

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使用具有碱性官能团的环状α，α-二取代α-氨基酸的细胞穿透肽

在细胞不可渗透分子的递送中，作为细胞内递送工具的细胞穿透肽（CPP）已引起越来越多的关注。在本研究中，我们设计了五种在五元环上具有碱性官能团且在α位上具有不同手性的环状α，α-二取代α-氨基酸（dAAs），并将其引入精氨酸（Arg）-丰富的肽。细胞穿透能力的评估表明，这些肽表现出比Arg九肽更好的细胞渗透性。此外，含有dAA的肽比具有较长孵育时间的市售转染试剂更好地递送了质粒DNA（pDNA）。