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Mechanisms of Peptide Amphiphile Internalization by SJSA-1 Cells in Vitro

机译:SJSA-1细胞体外肽两亲性内在化的机制

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摘要

Self-assembly of peptide amphiphiles into nanostructures makes them attractive for a varietynof applications in drug and peptide delivery. We here report on the interactions of micelles composed ofna palmitoylated, pro-apoptotic peptide derived from p53 tumor suppressor protein with a human cancerncell line. Characterization of self-assembly in aqueous buffered solutions revealed formation of elongatednrod-like micelles above a critical micelle concentration. Our results however demonstrate that monomersninstead of micelles are internalized, a finding that correlates with the dynamic nature of the assembliesnand the noncovalent interactions that hold them together. Internalization is shown to occur via adsorptionmediated,nenergy-dependent pathways, resulting in accumulation of the material in endocytic vesicles.nWe conclude that palmitoylation of peptides is an efficient way to increase peptide permeability insidenSJSA-1 cells and that increased micelle stability would be required for intact micelle internalization.
机译:肽两亲物自组装成纳米结构使它们对于药物和肽递送中的多种应用具有吸引力。我们在此报告了由p53肿瘤抑制蛋白衍生的棕榈酰化,促凋亡肽组成的微团与人类癌细胞的相互作用。在水性缓冲溶液中自组装的特征表明,在临界胶束浓度以上会形成细长棒状胶束。然而,我们的结果表明单体而非胶束被内化了,这一发现与组装体的动态性质以及将它们结合在一起的非共价相互作用相关。研究表明内在化是通过吸附介导的,依赖于能量的途径发生的,导致内吞小泡中物质的积累。n我们得出结论,肽的棕榈酰化是增加SJSA-1细胞内部肽通透性的有效方法,因此需要增加胶束的稳定性完整的胶束内部化。

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  • 来源
    《Biochemistry》 |2009年第15期|p.3304-3314|共11页
  • 作者单位

    Department of Chemical Engineering and Materials Departments and Materials Research Laboratory, UniVersity of California,Santa Barbara, California 93106, and National Center for Macromolecular Imaging, Department of Biochemistry andMolecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030ReceiVed December 24, 2008, ReVised Manuscript ReceiVed February 25, 2009,;

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