Guler Mustafa O, Hsu Lorraine, Soukasene Stephen, Harrington Daniel A, Hulvat James F, Stupp Samuel I
Department of Chemistry, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, USA.
Biomacromolecules. 2006 Jun;7(6):1855-63. doi: 10.1021/bm060161g.
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.
利用赖氨酸残基上胺基的正交保护基团化学方法，设计并合成了带有生物表位的支链肽两亲分子（PA）。这些分子自组装成高纵横比的圆柱形纳米纤维，其支链结构增强了表位与蛋白质结合的可及性，并且还能在单个分子中呈现多个表位。RGDS细胞黏附表位被用作PA分子上的模型生物活性信号，用于潜在的生物医学应用。通过透射电子显微镜（TEM）以及外周胺质子化谱的变化，证明了支链PA分子聚集形成纳米纤维。在生理流体和其他生物相关大分子（如滑液和DNA）存在的情况下，这些体系还形成了自支撑凝胶，这是它们在医学上潜在应用的一个重要特性。对带有色氨酸残基的PA进行荧光各向异性测量，以研究支链对自组装纳米纤维中肽的堆积和流动性的影响。观察到当PA分子堆积成纳米纤维时，色氨酸残基的流动性受到限制。然而，相对于线性类似物，支链分子在超分子聚集体中保留了更多的流动性。
