Gros Edwige, Deshayes Sebastien, Morris May C, Aldrian-Herrada Gudrun, Depollier Julien, Heitz Frederic, Divita Gilles
Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, Department of Molecular Biophysics and Therapeutic, 1919 Route de Mende, 34293 Montpellier, France.
Biochim Biophys Acta. 2006 Mar;1758(3):384-93. doi: 10.1016/j.bbamem.2006.02.006. Epub 2006 Mar 3.
The development of therapeutic peptides and proteins is limited by the poor permeability and the selectivity of the cell membrane. The discovery of protein transduction domains has given a new hope for administration of large proteins and peptides in vivo. We have developed a non-covalent strategy for protein transduction based on an amphipathic peptide, Pep-1, that consists of a hydrophobic domain and a hydrophilic lysine-rich domain. Pep-1 efficiently delivers a variety of fully biologically active peptides and proteins into cells, without the need for prior chemical cross-linking or chemical modifications. The mechanism through which Pep-1 delivers active macromolecules does not involve the endosomal pathway and the dissociation of the Pep-1/macromolecule particle occurs immediately after it crosses the cell membrane. Pep-1 has been successfully applied to the screening of therapeutic peptides in vivo and presents several advantages: stability in physiological buffer, lack of toxicity and of sensitivity to serum. In conclusion, Pep-1 technology could contribute significantly to the development of fundamental and therapeutic applications and be an alternative to covalent protein transduction domain-based technologies.
治疗性肽和蛋白质的开发受到细胞膜通透性差和选择性的限制。蛋白质转导结构域的发现为体内施用大蛋白质和肽带来了新希望。我们基于一种两亲性肽Pep-1开发了一种非共价蛋白质转导策略，Pep-1由一个疏水域和一个富含赖氨酸的亲水域组成。Pep-1能有效地将多种具有完全生物活性的肽和蛋白质递送至细胞内，无需事先进行化学交联或化学修饰。Pep-1递送活性大分子的机制不涉及内体途径，且Pep-1/大分子颗粒在穿过细胞膜后立即发生解离。Pep-1已成功应用于体内治疗性肽的筛选，并具有以下几个优点：在生理缓冲液中稳定、无毒且对血清不敏感。总之，Pep-1技术可为基础和治疗应用的开发做出重大贡献，并成为基于共价蛋白质转导结构域技术的替代方法。
