Presentation of RGDS epitopes on self-assembled nanofibers of branched peptide amphiphiles
Presentation of RGDS epitopes on self-assembled nanofibers of branched peptide amphiphiles
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DOI：
10.1021/bm060161g
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发表时间：
2006-06-01
影响因子：
6.2
通讯作者：
Stupp, Samuel I.
中科院分区：
文献类型：
--
作者：
Guler, Mustafa O.;Hsu, Lorraine;Stupp, Samuel I.
利用正交保护基化学法设计合成了具有生物表位的支链肽两亲物（PA）分子。这些分子自组装成高纵横比的圆柱形纳米纤维，并且它们的分支结构增强了用于蛋白质结合的表位的可及性，并且还允许在单个分子中呈现多于一个表位。RGDS细胞粘附表位被用作PA分子上潜在生物医学应用的模型生物活性信号。通过TEM和外围胺的质子化曲线的变化证明了分支PA分子聚集成纳米纤维。这些系统还在生理液体和其他生物相关大分子（如滑液和DNA）存在下形成自支撑凝胶，这是其在医学中潜在用途的重要性质。对具有色氨酸残基的PA进行荧光各向异性测量，以检查支化对自组装纳米纤维中肽的填充和流动性的影响。观察到色氨酸残基的流动性在PA分子包装成纳米纤维后受到限制。然而，相对于线性类似物，支化分子在超分子聚集体中保留更多的流动性。
Branched peptide amphiphile (PA) molecules bearing biological epitopes were designed and synthesized using orthogonal protecting group chemistry on amine groups at lysine residues. These molecules self-assemble into high-aspect-ratio cylindrical nanofibers, and their branched architecture enhances accessibility of epitopes for protein binding and also allows the presentation of more than one epitope in a single molecule. The RGDS cell adhesion epitope was used as a model bioactive signal on PA molecules for potential biomedical applications. Aggregation of the branched PA molecules into nanofibers was demonstrated by TEM and through shifts in the protonation profiles of peripheral amines. These systems also formed self-supporting gels in the presence of physiological fluids and other biologically relevant macromolecules such as synovial fluid and DNA, an important property for their potential use in medicine. Fluorescence anisotropy measurements on the PAs with tryptophan residues were performed to examine the effect of branching on packing and mobility of the peptides in the self-assembled nanofibers. The mobility of tryptophan residues was observed to be restricted upon packing of PA molecules into nanofibers. However, relative to linear analogues, branched molecules retain more mobility in the supramolecular aggregates.