Cellular uptake of an α-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically
Cellular uptake of an α-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically
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DOI：
10.1016/s0005-2736(98)00161-8
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发表时间：
1998-11-11
影响因子：
3.4
通讯作者：
Bienert, M
中科院分区：
文献类型：
--
作者：
Oehlke, J;Scheller, A;Bienert, M
证据表明哺乳动物细胞摄取 α 螺旋两亲性模型肽 FLUOS-KLALKLALKALKAALKLA-NH2 (I) 涉及多种可能非内吞机制。 I 的 N 端 GC 延长衍生物被广泛的细胞摄取，通过二硫桥与不同电荷的肽缀合，表明 I 样模型肽可以作为极性生物活性化合物的细胞内递送的载体。 I 的细胞内化模式包括能量、温度、pH 和离子依赖性以及非依赖性过程，这表明与先前报道的小非结构化肽所显示的相似（Oehlke 等人，Biochim. Biophys. Acta 1330 (1997) 50-60)。 I的摄取行为也显示出与几种蛋白质衍生的螺旋肽序列的相似性，最近发现它们能够有效地将标记的寡核苷酸和肽直接携带到哺乳动物细胞的胞质溶胶中（Derossi等人，J. Biol. Chem. 269 (1994) 10444-10450；Lin等人，J. Biol. Chem. 270 (1995) 14255-14258；Proc.Natl.Sci.91(1994)663-668；Chaloin 等人，Biochemistry 36(1997)11179-11187；Vives 等人，J.Biol。 16010-16017）。 (C) 1998 Elsevier Science B.V. 保留所有权利。
Evidence that multiple, probably non-endocytic mechanisms are involved in the uptake into mammalian cells of the alpha-helical amphipathic model peptide FLUOS-KLALKLALKALKAALKLA-NH2 (I) is presented. Extensive cellular uptake of N-terminally GC-elongated derivatives of I, conjugated by disufide bridges to differently charged peptides, indicated that I-like model peptides might serve as vectors for intracellular delivery of polar bioactive compounds. The mode of the cellular internalization of I comprising energy-, temperature- pH- and ion-dependent as well as -independent processes suggests analogy to that displayed by small unstructured peptides reported previously (Oehlke et al., Biochim. Biophys. Acta 1330 (1997) 50-60). The uptake behavior of I also showed analogy to that of several protein-derived helical peptide sequences, recently found to be capable of efficiently carrying tagged oligonucleotides and peptides directly into the cytosol of mammalian cells (Derossi et al., J. Biol. Chem. 269 (1994) 10444-10450; Lin et al., J. Biol. Chem. 270 (1995) 14255-14258; Fawell et al., proc. Natl. Acad. Sci. USA 91 (1994) 663-668; Chaloin ct al., Biochemistry 36 (1997) 11179-11187; Vives et al., J. Biol. Chem., 272 (1997) 16010-16017). (C) 1998 Elsevier Science B.V. All rights reserved.