Chang Willy M, Dakanali Marianna, Capule Christina C, Sigurdson Christina J, Yang Jerry, Theodorakis Emmanuel A
Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC: 0358, La Jolla, CA 92093-0358, USA.
ACS Chem Neurosci. 2011 May 18;2(5):249-255. doi: 10.1021/cn200018v.
A new family of fluorescent markers containing an Amino Naphthalenyl-2-Cyano-Acrylate (ANCA) motif has been synthesized and evaluated for its capability to associate with aggregated β-amyloid (Aβ) peptides. These fluorescent probes contain a nitrogen donor group that is connected via a naphthalene unit to an electron acceptor motif containing Water Solubilizing Groups (WSG). Chemical modifications were introduced to explore their effect on the capability of the ANCA-based probes to fluorescently label aggregated Aβ peptides. All synthesized probes bind to aggregated Aβ fibrils with low micromolar affinity and fluorescently stain amyloid deposits in human brain tissue from patients with Alzheimer's disease. We found that structural modifications of the WSG site do not affect considerably the binding affinity. However, changes of the nitrogen donor group alter significantly the binding affinity of these probes. Also, increasing the hydrophilicity of the donor group leads to improved contrast between the Aβ deposits and the surrounding tissue in histological staining experiments.
一种含有氨基萘基-2-氰基丙烯酸酯（ANCA）基序的新型荧光标记物家族已被合成，并对其与聚集的β-淀粉样蛋白（Aβ）肽结合的能力进行了评估。这些荧光探针含有一个氮供体基团，该基团通过萘单元连接到一个含有水溶性基团（WSG）的电子受体基序上。引入化学修饰以探究其对基于ANCA的探针荧光标记聚集Aβ肽能力的影响。所有合成的探针都以低微摩尔亲和力与聚集的Aβ纤维结合，并对阿尔茨海默病患者的人脑组织中的淀粉样沉积物进行荧光染色。我们发现WSG位点的结构修饰对结合亲和力没有显著影响。然而，氮供体基团的变化会显著改变这些探针的结合亲和力。此外，增加供体基团的亲水性会导致组织学染色实验中Aβ沉积物与周围组织之间的对比度提高。
