The photolytic activity of poly-arginine cell penetrating peptides conjugated to carboxy-tetramethylrhodamine is modulated by arginine residue content and fluorophore conjugation site.
The photolytic activity of poly-arginine cell penetrating peptides conjugated to carboxy-tetramethylrhodamine is modulated by arginine residue content and fluorophore conjugation site.
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DOI：
10.1111/php.12288
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发表时间：
2014-09
影响因子：
3.3
通讯作者：
Pellois JP
中科院分区：
文献类型：
--
作者：
Muthukrishnan N;Donovan S;Pellois JP
在光照射下，荧光团-CPP偶联物会破坏生物膜的完整性。这种活性反过来可以用来光诱导内吞细胞器的破坏，并促进被包裹的大分子，如蛋白质或RNA进入活细胞。最近的机理研究表明，荧光团产生的ROS和CPPs的潜在裂解能力协同作用，引发光解。然而，荧光团-CPP偶联物的结构如何影响这种协同活性仍不清楚。在这里，我们使用红细胞作为生物膜的模型，我们证明了CPP中精氨酸残基的数量以及荧光团相对于CPP的位置显著地影响了荧光团-CPP结合物的光解活性。因此，在开发有效的光诱导递送剂时，应考虑这些因素。
Upon light irradiation, fluorophore-CPP conjugates can disrupt the integrity of biological membranes. This activity can in turn be used to photo-induce the disruption of endocytic organelles and promote the delivery of entrapped macromolecules such as proteins or RNAs into live cells. Recent mechanistic studies have shown that ROS production by the fluorophore and a latent lytic ability of CPPs act in synergy to elicit photolysis. However, how the structure of fluorophore-CPP conjugates impacts this synergistic activity remains unclear. Herein, using red blood cells as a model of biological membranes, we show that the number of arginine residues in a CPP as well as the position of fluorophore with respect to the CPP dramatically affect the photolytic activity of a fluorophore-CPP conjugate. These factors should therefore be considered for the development of effective photo-inducible delivery agents.