Design and Synthesis of 6-O-Phosphorylated Heparan Sulfate Oligosaccharides to Inhibit Amyloid β Aggregation.
Design and Synthesis of 6-O-Phosphorylated Heparan Sulfate Oligosaccharides to Inhibit Amyloid β Aggregation.
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DOI：
10.1002/cbic.202200191
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发表时间：
2022-08-03
期刊：
影响因子：
3.2
通讯作者：
Hung, Shang-Cheng
中科院分区：
文献类型：
--
作者：
Uchimura, Kenji;Nishitsuji, Kazuchika;Chiu, Li-Ting;Ohgita, Takashi;Saito, Hiroyuki;Allain, Fabrice;Gannedi, Veeranjaneyulu;Wong, Chi-Huey;Hung, Shang-Cheng
淀粉样蛋白的失调及其在组织中的异常加工和沉积会导致系统性和局部淀粉样变性。 β 淀粉样蛋白 (Aβ) 原纤维的形成作为淀粉样斑块沉积在阿尔茨海默病 (AD) 大脑中，是最早的病理标志。多硫酸乙酰肝素 (HS)/肝素 (HP) 是 Aβ 沉积物的非蛋白质成分之一，不仅可以调节 Aβ 聚集，还可以作为 Aβ 原纤维的受体来介导其细胞毒性。干扰 HS/HP 和 Aβ 之间的相互作用可能是阻止淀粉样变性的一种治疗策略。在这里，我们合成了 6-O-磷酸化 HS/HP 寡糖，并使用硫黄素 T 荧光测定和轻敲模式原子力显微镜报告了它们对体外抑制 HP 介导的 Aβ 原纤维形成的竞争作用。 合理设计并合成了6-O-磷酸化硫酸乙酰肝素四糖，以在体外抑制肝素诱导的β淀粉样蛋白（Aβ）的淀粉样原纤维形成。硫代黄素 T 荧光测定和轻敲模式原子力显微镜证实了其竞争效应。
Dysregulation of amyloidogenic proteins and their abnormal processing and deposition in tissues cause systemic and localized amyloidosis. Formation of amyloid β (Aβ) fibrils that deposit as amyloid plaques in Alzheimer's disease (AD) brains is an earliest pathological hallmark. The polysulfated heparan sulfate (HS)/heparin (HP) is one of the non‐protein components of Aβ deposits that not only modulates Aβ aggregation, but also acts as a receptor for Aβ fibrils to mediate their cytotoxicity. Interfering with the interaction between HS/HP and Aβ could be a therapeutic strategy to arrest amyloidosis. Here we have synthesized the 6‐O‐phosphorylated HS/HP oligosaccharides and reported their competitive effects on the inhibition of HP‐mediated Aβ fibril formation in vitro using a thioflavin T fluorescence assay and a tapping mode atomic force microscopy. A 6‐O‐phosphorylated heparan sulfate tetrasaccharide was rationally designed and synthesized to inhibit heparin‐induced amyloid fibril formation of amyloid β (Aβ) in vitro. Its competitive effect was confirmed by a thioflavin T fluorescence assay and a tapping mode atomic force microscopy.
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DOI：
10.1016/j.bbrc.2020.11.092
发表时间：
2021-01-01
影响因子：
3.1
作者：
Gu L;Guo Z
通讯作者：
Guo Z
影响因子：
2.8
作者：
de Paz, JL;Martin-Lomas, M
通讯作者：
Martin-Lomas, M
影响因子：
15
作者：
Chiu, Li-Ting;Sabbavarapu, Narayana Murthy;Hung, Shang-Cheng
通讯作者：
Hung, Shang-Cheng
影响因子：
4.8
作者：
Jose Valle-Delgado, Juan;Alfonso-Prieto, Mercedes;Fernandez-Busquets, Xavier
通讯作者：
Fernandez-Busquets, Xavier
DOI：
10.3390/molecules20022510
发表时间：
2015-02-02
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Iannuzzi C;Irace G;Sirangelo I
通讯作者：
Sirangelo I