Effects of cell-permeating peptide binding on the distribution of 125I-labeled Fab fragment in rats
Effects of cell-permeating peptide binding on the distribution of 125I-labeled Fab fragment in rats
复制标题
DOI：
10.1021/bc050258k
复制
发表时间：
2006-05-17
影响因子：
4.7
通讯作者：
Futaki, S
中科院分区：
文献类型：
--
作者：
Kameyama, S;Horie, M;Futaki, S
已知由HIV-1Tat蛋白序列(第48-60位)、触角蛋白序列(第43-58位)和HIV-1Rev蛋白序列(第34-50位)组成的多肽具有细胞渗透性。在这项研究中，我们研究了Fab片段在大鼠体内的分布如何受到这些肽的结合的影响。用氯胺-T法对Fab片段进行碘化，然后与细胞渗透肽进行化学偶联。给雄性大鼠静脉注射I-125-Fab与细胞渗透肽的复合体1 mg/kg，分别于给药后4 h和24 h进行全身放射自显影。I-125-Fab的分布模式因所使用的细胞渗透肽的不同而有显著差异。尤其是在4h时，REV肽-Fab复合体在脾、肾上腺、肾髓质和肝脏，TAT肽-Fab复合体在肝脏和脾，在脾、肾上腺和肝脏中观察到较高浓度的放射性。即使在24小时，REV肽-Fab复合体仍能在大鼠的脾和肾髓质中观察到较高的放射性，而在Antennapedia多肽-Fab复合体的大鼠的脾和肾皮质中仍能观察到较高浓度的放射性。这些发现表明，多肽-I-125-Fab复合体的分布模式可以通过选择细胞穿透性多肽来调节。此外，在给药后24小时，多肽-I-125-Fab复合体在内脏器官中的滞留模式也不同。这些发现为开发新型抗体药物和治疗系统提供了有价值的信息。
The peptides comprising the sequence of HIV-1 Tat protein (positions 48-60), Antennapedia (positions 43-58), and HIV-1 Rev protein (positions 34-50) are known to be cell-permeating. In this study, we examined how the distribution of Fab fragments in rats is affected by conjugation with these peptides. Fab fragment was iodinated by a chloramine-T method and then chemically conjugated with cell-permeating peptide. The complex of I-125-Fab and cell-permeating peptide was administered to male rats intravenously at a dose of 1 mg/kg, and whole-body autoradiography was performed at 4 and 24 h after administration. The patterns of distribution of I-125-Fab exhibited remarkable variation depending on the cell-permeating peptide used. In particular, at 4 h, high concentrations of radioactivity were observed in the spleen, adrenal gland, renal medulla, and liver with Rev peptide-Fab complex, in the liver and spleen with Tat peptide-Fab complex, and in the spleen, adrenal gland, and liver with Antennapedia peptide-Fab complex. Even at 24 h, high concentrations of radioactivity were still observed in the spleen and renal medulla of rat with Rev peptide-Fab complex, and in the spleen and renal cortex of rat with Antennapedia peptide-Fab complex. These findings demonstrate that the patterns of distribution of peptide-I-125-Fab complexes can be modulated by selection of cell-penetrating peptides. Moreover, the patterns of retention of peptide-I-125-Fab complexes in internal organs also differed at 24 h after administration. These findings provide valuable information for the development of novel antibody pharmaceuticals and therapeutic systems.