Synergy between cell-penetrating peptides and singlet oxygen generators leads to efficient photolysis of membranes.

Synergy between cell-penetrating peptides and singlet oxygen generators leads to efficient photolysis of membranes.
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DOI:
10.1111/php.12036
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发表时间:
2013-05
影响因子:
3.3
通讯作者:
Pellois JP
Pellois JP
中科院分区:
生物学3区
文献类型:
--
作者:
Muthukrishnan N;Johnson GA;Erazo-Oliveras A;Pellois JP

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用小的有机荧光团标记的细胞穿透肽如达特或R9可以在光照射时裂解内体。这些化合物的光内体溶解活性又可用于在空间和时间控制下将蛋白质和核酸递送至活细胞的胞质溶胶。在这份报告中,我们研究的机制,这样的荧光肽发挥光解活性使用红细胞作为膜模型。我们表明,用四甲基罗丹明标记的肽达特和R9通过促进在细胞膜附近形成单线态氧来光解红细胞。此外,未标记达特和R9加速反式膜结合光敏剂虎红的光解活性,表明细胞穿透肽参与光氧化膜的不稳定化。因此,肽和单线态氧发生剂协同作用,在照射时破坏膜。
Cell-penetrating peptides such as TAT or R9 labeled with small organic fluorophores can lyse endosomes upon light irradiation. The photo-endosomolytic activity of these compounds can in turn be used to deliver proteins and nucleic acids to the cytosol of live cells with spatial and temporal control. In this report, we examine the mechanisms by which such fluorescent peptides exert a photolytic activity using red blood cells as a membrane model. We show that the peptides TAT and R9 labeled with tetramethylrhodamine photolyse red blood cells by promoting the formation of singlet oxygen in the vicinity of the cells’ membranes. In addition, unlabeled TAT and R9 accelerate the photolytic activity of the membrane-bound photosensitizer Rose Bengal in trans, suggesting that the cell-penetrating peptides participate in the destabilization of photo-oxidized membranes. Peptides and singlet oxygen generators therefore act in synergy to destroy membranes upon irradiation.
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