Baylor All Saints Medical Center, Baylor Research Institute, Fort Worth, TX 76104, USA.
Cell Transplant. 2010;19(6):649-54. doi: 10.3727/096368910X508744. Epub 2010 Jun 3.
During the past 15 years, a variety of peptides, known as protein transduction domains (PTDs), or cell-penetrating peptides (CPPs), have been characterized for their ability to translocate into live cells. There are now numerous examples of biologically active full-length proteins and peptides that have been successfully delivered to cells and tissues, both in vitro and in vivo. One of the principal mechanisms of protein transduction is via electrostatic interactions with the plasma membrane, subsequent penetration into the cells by macropinocytosis, and release into the cytoplasm and nuclei by retrograde transport. Recent reports have also now shown that some of the limitations of protein transduction technology have been overcome. In particular, the use of ubiquitination-resistant proteins has been demonstrated to be a more effective strategy for transduction because the half-life of these molecules is significantly increased. Moreover, the use of the NH2-terminal domain of the influenza virus hemagglutinin-2 subunit (HA2) or photosensitive PTDs has been shown to specifically enhance macropinosome escape. Hence, these and other recent advances in protein transduction technologies have created a number of possibilities for the development of new peptide-based drugs.
在过去的 15 年中，已经有多种肽被鉴定具有穿过细胞膜进入活细胞的能力，这些肽被称为蛋白质转导结构域（PTDs）或细胞穿透肽（CPPs）。现在已经有许多例子表明，生物活性全长蛋白质和肽已经成功地递送到细胞和组织中，无论是在体外还是体内。蛋白质转导的主要机制之一是通过与质膜的静电相互作用，随后通过巨胞饮作用进入细胞，并通过逆行运输释放到细胞质和核内。最近的报告还表明，已经克服了蛋白质转导技术的一些限制。特别是，使用抗泛素化蛋白已被证明是一种更有效的转导策略，因为这些分子的半衰期显著增加。此外，已经表明流感病毒血凝素-2 亚基（HA2）的 NH2 末端结构域或光敏 PTD 的使用可以特异性地增强巨胞饮体逃逸。因此，这些和蛋白质转导技术的其他最新进展为开发新的基于肽的药物创造了许多可能性。
