Self-Assembly of PEGylated Peptide Conjugates Containing a Modified Amyloid β-Peptide Fragment

Self-Assembly of PEGylated Peptide Conjugates Containing a Modified Amyloid β-Peptide Fragment
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DOI:
10.1021/la100110f
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发表时间:
2010-06-15
期刊:
影响因子:
3.9
通讯作者:
Noirez, L.
Noirez, L.
中科院分区:
化学2区
文献类型:
--
作者:
Castelletto, V.;Newby, G. E.;Noirez, L.

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已经在水溶液中研究了含有来自淀粉样β肽FEK LVFF的修饰序列的聚乙二醇化肽的自组装。缀合物中使用 PEG 摩尔质量 PEG1k、PEG2k 和 PEG10k。结果表明,三种 FFK LVFF-PEG 杂化物形成包含 FFKLVFF 核心和 PEG 冠的原纤维。肽的 β-折叠二级结构保留在 FFK LVFF 原纤维核心中。在足够高的浓度下,FEK LVFF-PEG1k 和 FEK LVFF-PEG2k 形成向列相,而 PEG10k-FEK LVFF 呈现六方柱状相。同时进行小角度中子散射/剪切流实验,以研究向列相和六方液晶相的剪切流排列。干燥时,PEG 结晶不会破坏 FFK LVFF β-折叠结构,从而在 X 射线衍射图和 FTIR 光谱中出现特征峰。还研究了 FFKLVFF-PEG 缀合物与聚丙烯酸 (PAA) 混合物中 β-折叠结构的稳定性。虽然共混物中 PAA 含量高达 25% 时才观察到 PEG 结晶,但 PAA 含量高达 75% 时,FFK LVFF β-折叠结构得以保留。
The self-assembly of PEGylated peptides containing a modified sequence from the amyloid beta peptide, FEK LVFF, has been studied in aqueous solution. PEG molar masses PEG1k, PEG2k, and PEG10k were used in the conjugates. It is shown that the three FFK LVFF-PEG hybrids form fibrils comprising a FFKLVFF core and a PEG corona. The beta-sheet secondary structure of the peptide is retained in the FFK LVFF fibril core. At sufficiently high concentrations, FEK LVFF-PEG1k and FEK LVFF-PEG2k form a nema tic phase, while PEG10k-FEK LVFF exhibits a hexagonal columnar phase. Simultaneous small angle neutron scattering/shear flow experiments were performed to study the shear flow alignment of the nematic and hexagonal liquid crystal phases. On drying, PEG crystallization occurs without disruption of the FFK LVFF beta-sheet structure leading to characteristic peaks in the X-ray diffraction pattern and FTIR spectra. The stability of beta-sheet structures was also studied in blends of FFKLVFF-PEG conjugates with poly(acrylic acid) (PAA). While PEG crystallization is only observed up to 25% PAA content in the blends, the FFK LVFF beta-sheet structure is retained up to 75% PAA.