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Shortened Penetratin Cell-Penetrating Peptide Is Insufficient for Cytosolic Delivery of a Grb7 Targeting Peptide
ACS Omega ( IF 3.7 ) Pub Date : 2017-02-23 00:00:00 , DOI: 10.1021/acsomega.6b00561 Gabrielle M. Watson 1 , Ketav Kulkarni 1 , Rebecca Brandt 1 , Mark P. Del Borgo 1 , Marie-Isabel Aguilar 1 , Jacqueline A. Wilce 1
ACS Omega ( IF 3.7 ) Pub Date : 2017-02-23 00:00:00 , DOI: 10.1021/acsomega.6b00561 Gabrielle M. Watson 1 , Ketav Kulkarni 1 , Rebecca Brandt 1 , Mark P. Del Borgo 1 , Marie-Isabel Aguilar 1 , Jacqueline A. Wilce 1
Affiliation
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Delivery across the cell membrane is of critical importance for the development of therapeutics targeting intracellular proteins. The use of cell-penetrating peptides (CPPs), such as Penetratin (P16), has facilitated the delivery of otherwise cell-impermeable molecules allowing them to carry out their biological function. A truncated form of Penetratin (RRMKWKK) has been previously described as the minimal Penetratin sequence that is required for translocation across the cell membrane. Here, we performed a detailed comparison of cellular uptake by Penetratin (P16) and the truncated Penetratin peptide (P7), including their ability to deliver G7-18NATE, a cyclic peptide targeting the cytosolic cancer target Grb7-adapter protein into cells. We identified that both P16 and P7 were internalized by cells to comparable levels; however, only P16 was effective in delivering G7-18NATE to produce a biological response. Live-cell imaging of fluorescein isothiocyanate-labeled peptides suggested that while P7 may be taken up into cells, it does not gain access to the cytosolic compartment. Thus, this study has identified that the P7 peptide is a poor CPP for the delivery of G7-18NATE and may also be insufficient for the intracellular delivery of other bioactive molecules.
中文翻译：
缩短的Penetratin细胞穿透肽不足以用于Grb7靶向肽的胞质传递。
跨细胞膜的递送对于靶向细胞内蛋白的治疗剂的开发至关重要。细胞渗透性肽（CPP）的使用，例如渗透肽（Pnetratin（P16）），已经促进了其他细胞不渗透性分子的递送，从而使其能够发挥其生物学功能。Penetratin（RRMKWKK）的截短形式以前已被描述为跨细胞膜易位所需的最小Penetratin序列。在这里，我们进行了Penetratin（P16）和截短的Penetratin肽（P7）对细胞摄取的详细比较，包括它们将G7-18NATE（一种靶向胞浆癌靶标Grb7-衔接蛋白的环肽）递送到细胞中的能力。我们发现P16和P7均被细胞内在化至可比水平。然而，仅P16有效递送G7-18NATE以产生生物学应答。荧光素异硫氰酸酯标记的肽的活细胞成像显示，尽管P7可能被细胞吸收，但无法进入胞质区室。因此，这项研究已经确定，P7肽对于G7-18NATE的递送而言是差的CPP，对于其他生物活性分子的细胞内递送也可能不足。
更新日期：2017-02-23
中文翻译：
缩短的Penetratin细胞穿透肽不足以用于Grb7靶向肽的胞质传递。
跨细胞膜的递送对于靶向细胞内蛋白的治疗剂的开发至关重要。细胞渗透性肽（CPP）的使用，例如渗透肽（Pnetratin（P16）），已经促进了其他细胞不渗透性分子的递送，从而使其能够发挥其生物学功能。Penetratin（RRMKWKK）的截短形式以前已被描述为跨细胞膜易位所需的最小Penetratin序列。在这里，我们进行了Penetratin（P16）和截短的Penetratin肽（P7）对细胞摄取的详细比较，包括它们将G7-18NATE（一种靶向胞浆癌靶标Grb7-衔接蛋白的环肽）递送到细胞中的能力。我们发现P16和P7均被细胞内在化至可比水平。然而，仅P16有效递送G7-18NATE以产生生物学应答。荧光素异硫氰酸酯标记的肽的活细胞成像显示，尽管P7可能被细胞吸收，但无法进入胞质区室。因此，这项研究已经确定，P7肽对于G7-18NATE的递送而言是差的CPP，对于其他生物活性分子的细胞内递送也可能不足。
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