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Synthesis of methoxy-X04 derivatives and their evaluation in alzheimer's disease pathology

机译：甲氧基-X04衍生物的合成及其在阿尔茨海默氏病病理学中的评估

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Background: Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages. Objective: The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology. Methods and Results: In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay. Conclusion: This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.
机译：背景：阿尔茨海默氏病的特征是大脑中存在两种臭名昭著的蛋白质聚集体：主要由淀粉样β肽和tau蛋白衍生的细胞内成对螺旋丝组成的细胞外老年斑。诊断方法的敏感性和特异性不足，无法在所有疾病阶段将这些病理学标志形象化，从而损害了阿尔茨海默氏病的诊断。目的：已建立的荧光标记物甲氧基-X04以良好的特异性染色斑块，tau缠结和淀粉样蛋白衍生的血管病变，但受到体内缓慢消除的限制。由于对新标记的需求很高，我们制备了甲氧基-X04衍生物，并评估了它们作为阿尔茨海默氏病病理学成像剂的潜力。方法和结果：在这项研究中，我们描述了一种改进的甲氧基-X04及其衍生物的合成方法，以及它们通过免疫组织学和置换测定法对各自蛋白质靶标的亲和力测定。结论：这导致鉴定了具有改善的结合亲和力的新的甲氧基-X04衍生物。

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