Wada Shun-ichi, Hitora Yasunari, Tanaka Reiko, Urata Hidehito
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Bioorg Med Chem Lett. 2008 Jul 15;18(14):3999-4001. doi: 10.1016/j.bmcl.2008.06.005. Epub 2008 Jun 6.
The biophysical characteristics and channel-forming activity of peptaibols inserted into artificial membranes have been studied over the last 30 years. However, to our knowledge, no studies have addressed directly their behavior in living cells. In this work, a novel strategy has been employed to precisely assess the living cell membrane-penetrating activity of a fluorescein-labeled Aib (alpha-aminoisobutyric acid)-containing peptide derived from a peptaibol, trichorovin-XIIa (TV-XIIa). We have demonstrated for the first time that the peptide containing an unusual amino acid residue, Aib, is taken up by cells via a non endocytic pathway. The replacement of Aib in the TV-XIIa sequence with Ala inhibits the cellular uptake.
在过去30年里，人们对插入人工膜中的肽菌素的生物物理特性和通道形成活性进行了研究。然而，据我们所知，尚无研究直接涉及它们在活细胞中的行为。在这项工作中，我们采用了一种新策略来精确评估一种源自肽菌素trichorovin-XIIa（TV-XIIa）的、带有荧光素标记的含Aib（α-氨基异丁酸）肽的活细胞膜穿透活性。我们首次证明，含有不寻常氨基酸残基Aib的肽通过非内吞途径被细胞摄取。用Ala取代TV-XIIa序列中的Aib会抑制细胞摄取。
