The demand for highly efficient macromolecular drugs, used in the treatment of many severe diseases, is continuously increasing. However, the hydrophilic character and large molecular size of these drugs significantly limit their ability to permeate across cellular membranes and thus impede the drugs in reaching their target sites in the body. Cell-penetrating peptides (CPP) have gained attention as promising drug excipients, since they can facilitate drug permeation across cell membranes constituting a major biological barrier. Fluorophores are frequently covalently conjugated to CPPs to improve detection, however, the ensuing change in physico-chemical properties of the CPPs may alter their biological properties. With complementary biophysical techniques, we show that the mode of biomembrane interaction may change considerably upon labeling of the CPP penetratin (PEN) with a fluorophore. Fluorophore-PEN conjugates display altered modes of membrane interaction with increased insertion into the core of model cell membranes thereby exerting membrane-thinning effects. This is in contrast to PEN, which localizes along the head groups of the lipid bilayer, without affecting the thickness of the lipid tails. Particularly high membrane disturbance is observed for the two most hydrophobic PEN conjugates; rhodamine B or 1-pyrene butyric acid, as compared to the four other tested fluorophore-PEN conjugates.

中文翻译：

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细胞穿透肽的荧光团标记显着改变了生物膜相互作用的方式和程度。

用于治疗许多严重疾病的高效大分子药物的需求正在不断增加。但是，这些药物的亲水性和大分子大小极大地限制了它们渗透到细胞膜上的能力，从而阻碍了药物到达体内的靶位。细胞穿透肽（CPP）作为有希望的药物赋形剂已经引起了人们的注意，因为它们可以促进药物跨细胞膜的渗透，从而构成主要的生物屏障。荧光团通常与CPP共价偶联以改善检测，但是，随之而来的CPP物理化学性质的变化可能会改变其生物学性质。借助互补的生物物理技术，我们表明，用荧光团标记CPP渗透素（PEN）后，生物膜相互作用的模式可能会发生很大变化。荧光团-PEN偶联物显示出改变的膜相互作用模式，并增加了向模型细胞膜核心的插入，从而发挥了膜变薄的作用。这与PEN沿脂质双分子层的头基定位，而不影响脂质尾巴的厚度相反。对于两种疏水性最强的PEN共轭物，观察到特别高的膜扰动。罗丹明B或1-py丁酸，与其他四个测试的荧光团-PEN缀合物相比。荧光团-PEN偶联物显示出改变的膜相互作用模式，并增加了向模型细胞膜核心的插入，从而发挥了膜变薄的作用。这与PEN沿脂质双分子层的头基定位，而不影响脂质尾巴的厚度相反。对于两种疏水性最强的PEN共轭物，观察到特别高的膜干扰。罗丹明B或1-py丁酸，与其他四个测试的荧光团-PEN缀合物相比。荧光团-PEN偶联物显示出改变的膜相互作用模式，并增加了向模型细胞膜核心的插入，从而发挥了膜变薄的作用。这与PEN沿脂质双分子层的头基定位，而不影响脂质尾巴的厚度相反。对于两种疏水性最强的PEN共轭物，观察到特别高的膜干扰。罗丹明B或1-py丁酸，与其他四个测试的荧光团-PEN缀合物相比。