Conjugated polyelectrolytes -: Conformation-sensitive optical probes for staining and characterization of amyloid deposits
Conjugated polyelectrolytes -: Conformation-sensitive optical probes for staining and characterization of amyloid deposits
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DOI：
10.1002/cbic.200500550
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发表时间：
2006-07-01
期刊：
影响因子：
3.2
通讯作者：
Inganas, Olle
中科院分区：
文献类型：
--
作者：
Nilsson, K. Peter R.;Hammarstrom, Per;Inganas, Olle
与蛋白质聚集体沉积相关的疾病的特异性标志物引起了极大的兴趣。在这里，我们报告使用共轭聚电解质作为构象敏感的光学探针，用于组织标记的淀粉样蛋白沉积物在离体组织样本-淀粉样蛋白轻链在原发性系统性淀粉样变性，胰岛淀粉样蛋白多肽在人类胰腺，和A β淀粉样蛋白在阿尔茨海默氏病。在合适的条件下，这些探针特异性地结合淀粉样蛋白沉积物，这被看作是从淀粉样蛋白发射的橙红色。此外，当结合到不同的淀粉样蛋白沉积物或其他细胞内结构时，探针发出不同颜色的光。这种现象很可能是由于这些结构中蛋白质构象的差异。因此，不同的蛋白质构象将产生结合的DNA骨架的几何改变，从而提供来自结合的探针的不同发射。因此，构象敏感探针提供了光谱信号和蛋白质构象之间的直接联系。最后，探针也被证明是有用的离体荧光成像多声子激发。
Specific markers for diseases associated with protein aggregate depositions are of great interest. Here we report the use of conjugated polyelectrolytes as conformation-sensitive optical probes for histological labeling of amyloid deposits in ex vivo tissue samples - amyloid light chains in primary systemic amyloidosis, islet amyloid polypeptide in human pancreas, and A beta amyloid in Alzheimer's disease. Under suitable conditions, these probes bind specifically to amyloid deposits, and this is seen as an orange-red emission from the polyelectrolyte. Furthermore, the probes emit light of different colors when bound to different amyloid deposits or other intracellular structures. This phenomenon is most probably due to differences in the protein conformation in these structures. Hence, different protein conformations will generate geometric alterations of the bound polyelectrolyte backbone, affording different emissions from the bound probe. Conformation-sensitive probes thus provide a direct link between spectral signal and protein conformation. Finally, the probes also proved useful for ex vivo fluorescence imaging by multiphonon excitation.