Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK)). In vitro cytotoxicity and cellular uptake were characterized on HT-29 human colon carcinoma and HepG2 human hepatocarcinoma cell lines. Data indicate that the polycationic polypeptides studied are essentially nontoxic in the concentration range studied, and their uptake is very much dependent on the side chain structure (length, identity of amino acid X, and distance between the terminal positive charges) and also on the cell lines. Our findings in uptake inhibition studies suggest that predominantly macropinocytosis and caveole/lipid raft mediated endocytosis are involved. The efficacy of their internalization is markedly influenced by the hydrophobicity and charge properties of the amino acid X. Interestingly, the uptake properties of the these polypeptides show certain similarities to the entry pathways of several cell penetrating peptides.

中文翻译：

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带有聚[Lys]骨架的阳离子支链多肽的细胞吸收机制。

阳离子大分子载体可以是小分子化合物，药物，表位或核酸的有效载体。基于聚赖氨酸的聚合物支链多肽也已经在细胞和生物体水平上进行了系统的研究。在本研究中，我们报告了我们的发现，这些结果涉及具有（i）单氨基酸（poly [Lys（Xi）]，XiK）或（ii）寡聚体的阳离子侧链的9种结构相关的基于赖氨酸的多肽的细胞摄取特性[dl-丙氨酸]（poly [Lys（dl-Alam）]，AK）或（iii）寡聚[dl-丙氨酸]，在末端位置带有一个额外的氨基酸（X）（poly [Lys（Xi-dl-Alam） ）]（XAK））或（iv）靠近聚赖氨酸骨架的位置（poly [Lys（dl-Alam-Xi）]（AXK））。在HT-29人结肠癌和HepG2人肝癌细胞系中表征了体外细胞毒性和细胞摄取。数据表明，所研究的聚阳离子多肽在所研究的浓度范围内基本上是无毒的，它们的摄取在很大程度上取决于侧链结构（长度，氨基酸X的同一性以及末端正电荷之间的距离）以及细胞线。我们在吸收抑制研究中的发现表明，主要涉及巨胞饮作用和小孔/脂质筏介导的内吞作用。氨基酸X的疏水性和电荷性质显着影响其内在化的效力。有趣的是，这些多肽的摄取性质与几种细胞穿透肽的进入途径显示出某些相似性。