纤维涂料:一类淀粉样蛋白靶向肽

Julia Aragones Pedrola, Francoise A. Dekker, Katrin Guttmann, Litske M. van Leeuwen, Shalini Singh, Guy Mayer, Tommaso Garfagnini, Assaf Friedler, Stefan G.D. Rudiger
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引用次数: 0

摘要

阿尔茨海默病、帕金森病和亨廷顿斯病等神经退行性疾病的特征是淀粉样纤维的堆积,但这些疾病仍然无法治愈。开发早期诊断方法和改变疾病的疗法具有重要意义。最近,我们发现了一种可用于纤维诊断的特异性淀粉样蛋白粘合剂--FibrilPaint1 肽。在这里,我们介绍了一类能与蛋白纤维结合的 FibrilPaint1 衍生物。这些修饰包括电荷、末端和残基顺序的变化。因此,我们产生了一类具有一般纤维结合特性的多肽,并有可能进一步调整,如与多种染料连接、针对特定蛋白质和聚合体菌株进行优化,或针对靶向蛋白质降解策略进行调整。因此,"纤维素涂料 "多肽是一类很有前景的线索,可用于诊断和治疗淀粉样蛋白纤维。
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Fibril Paint: a class of amyloid-targeting peptides
Neurodegenerative diseases, such as Alzheimers Disease, Parkinsons Disease and Huntingtons Disease, are characterised by accumulation of amyloid fibrils, which remain incurable. It is of great importance to develop early-diagnosis approaches as well as disease-modifying therapies. Recently, we discovered the FibrilPaint1 peptide, a specific amyloid binder that can serve for fibril diagnosis. Here we introduce a class of FibrilPaint1 derivatives that bind to protein fibrils. The modifications include variation of the charge, termini and order of residues. As a result, we generated a class of peptides with general fibril-binding properties and with the potential for further adaptation, such as linkage to multiple dyes, optimisation for specific protein and aggregate strains, or adaptation for targeted protein degradation strategies. Thus, Fibril Paint peptides are a class of promising leads for targeting amyloid fibrils for diagnostic and therapeutic purposes.
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