Dissolution of amyloid aggregates by direct addition of alkali halides
Dissolution of amyloid aggregates by direct addition of alkali halides
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通过直接添加碱金属卤化物溶解淀粉样蛋白聚集体
DOI：
10.1016/j.molliq.2022.120849
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发表时间：
2023
影响因子：
6
通讯作者：
Yoshimura Yukihiro
中科院分区：
文献类型：
--
作者：
Takekiyo Takahiro;Yamada Natsuki;Amo Taku;Nakazawa Chikako T.;Asano Atushi;Ichimura Tohru;Kato Minoru;Yoshimura Yukihiro
淀粉样蛋白聚集体的标准溶出剂的开发对于获得药物治疗策略的基本信息和提高靶向表达蛋白的回收率至关重要。然而，目前没有标准的溶解剂应用于许多淀粉样蛋白聚集体。因此，为了进一步进行，使用直接添加碱金属卤化物研究在温和条件（pD 7.5和310 K）下形成的α-突触核蛋白淀粉样蛋白聚集体（α-突触核蛋白淀粉样蛋白）的溶解能力。傅里叶变换红外光谱和刚果红测定用于评价碱金属卤化物的溶解剂对淀粉样蛋白聚集体的效力。碱金属卤化物对α-突触核蛋白淀粉样蛋白的作用分为三种类型：（i）溶解作用，（ii）无作用，和（iii）促进作用。这些效应与阳离子的破坏能力（直接效应）和阳离子和阴离子之间的溶剂化自由能差（ΔΔGSolv）（间接效应）相关。值得注意的是，碘化锂（LiI）在所研究的碱金属卤化物中对α-突触核蛋白淀粉样蛋白具有最强的溶解能力。此外，透析可以从溶解在LiI中的α-突触核蛋白淀粉样蛋白恢复单体状态。此外，LiI对在极端条件下（pD 1.6和363 K）形成的牛胰岛素淀粉样蛋白聚集体也表现出很强的溶解能力。这些发现表明，LiI具有作为碱金属卤化物中淀粉样蛋白聚集体的标准溶解剂的潜力。
The development of standard dissolution agents for various amyloid aggregatesin vitrois essential to acquire basic information on pharmaceutical treatment strategies and improve the recovery rate for target expressed proteins. Nevertheless, no standard dissolution agents are currently applied to many amyloid aggregates. Thus, to proceed one step further, the dissolution ability of α-synuclein amyloid aggregates (α-synuclein amyloid) formed under mild conditions (pD 7.5 and 310 K) was investigated using the direct addition of alkali halides. Fourier-transform infrared spectroscopy and Congo red assay were used to evaluate the efficacy of the dissolution agents of alkali halides for amyloid aggregates. The effects of alkali halides on α- synuclein amyloid were classified into three types: (i) dissolution effect, (ii) no effect, and (iii) promotion effect. These effects correlate with the disruption ability of cations (the direct effect) and the solvation free energy difference (ΔΔGSolv) between the cations and anions (the indirect effect). Remarkably, lithium iodide (LiI) has the strongest dissolution ability for α-synuclein amyloid among the examined alkali halides. Furthermore, dialysis can recover the monomer state from α-synuclein amyloid dissolved in LiI. In addition, LiI also exhibits a strong dissolution ability for bovine insulin amyloid aggregates formed under extreme conditions (pD 1.6 and 363 K). These findings show that LiI has the potential as a standard dissolution agent applied to amyloid aggregates among the alkali halides.