Graduate School 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.
Sci Rep. 2019 Feb 4;9(1):1349. doi: 10.1038/s41598-018-38063-8.
Foldamers, which are folded oligomers with well-defined conformations, have been recently reported to have a good cell-penetrating ability. α,α-Disubstituted α-amino acids are one such promising tool for the design of peptide foldamers. Here, we prepared four types of L-arginine-rich nonapeptides containing L-leucine or α,α-disubstituted α-amino acids, and evaluated their secondary structures and cell-penetrating abilities in order to elucidate a correlation between them. Peptides containing α,α-disubstituted α-amino acids had similar resistance to protease digestion but showed different secondary structures. Intracellular uptake assays revealed that the helicity of peptides was important for their cell-penetrating abilities. These findings suggested that a peptide foldamer with a stable helical structure could be promising for the design of cell-penetrating peptides.
折叠体是具有明确构象的折叠寡聚物，最近有报道称它们具有良好的细胞穿透能力。α,α-二取代的α-氨基酸是设计肽折叠体的一种有前途的工具。在这里，我们制备了四种含有 L-亮氨酸或α,α-二取代的α-氨基酸的富含 L-精氨酸的九肽，并评估了它们的二级结构和细胞穿透能力，以阐明它们之间的相关性。含有α,α-二取代的α-氨基酸的肽对蛋白酶的消化具有相似的抗性，但表现出不同的二级结构。细胞内摄取实验表明，肽的螺旋性对于其细胞穿透能力很重要。这些发现表明，具有稳定螺旋结构的肽折叠体可能是设计细胞穿透肽的有前途的候选物。
