Deshayes Sébastien, Decaffmeyer Marc, Brasseur Robert, Thomas Annick
Centre de Biophysique Moléculaire Numérique (CBMN), Faculté Universitaire des Sciences Agronomiques de Gembloux, 2, Passage des Déportés, 5030 Gembloux, Belgium.
Biochim Biophys Acta. 2008 May;1778(5):1197-205. doi: 10.1016/j.bbamem.2008.01.027. Epub 2008 Feb 14.
Despite numerous investigations, the important structural features of Cell Penetrating Peptides (CPPs) remain unclear as demonstrated by the difficulties encountered in designing new molecules. In this study, we focused our interest on Penetratin and Transportan and several of their variants. Penetratin W48F and Penetratin W48F/W56F exhibit a reduced and a complete lack of cellular uptake, respectively; TP07 and TP10 present a similar cellular uptake as Transportan and TP08, TP13 and TP15 display no or weak internalization capacity. We applied the algorithmic method named PepLook to analyze the peptide polymorphism. The study reveals common conformational characteristics for the CPPs and their permeable variants: they all are polymorphic. Negative, non permeable, mutants share the opposite feature since they are monomorphic. Finally, we support the hypothesis that structural polymorphism may be crucial since it provides peptides with the possibility of adapting their conformation to medium hydrophobicity and or to partner diversity.
尽管进行了大量研究，但细胞穿透肽（CPPs）的重要结构特征仍不清楚，这从设计新分子时遇到的困难就可以看出。在本研究中，我们将兴趣集中在穿膜肽和转运蛋白及其几种变体上。穿膜肽W48F和穿膜肽W48F/W56F分别表现出细胞摄取减少和完全缺乏细胞摄取的情况；TP07和TP10的细胞摄取情况与转运蛋白相似，而TP08、TP13和TP15则没有或只有较弱的内化能力。我们应用名为PepLook的算法方法来分析肽的多态性。该研究揭示了CPPs及其可渗透变体的共同构象特征：它们都是多态的。阴性、不可渗透的突变体则具有相反的特征，因为它们是单态的。最后，我们支持这样一种假设，即结构多态性可能至关重要，因为它为肽提供了使其构象适应中等疏水性和/或伙伴多样性的可能性。
