Reevaluation of Copper(I) Affinity for Amyloid-ß Peptides by Competition with FerrozineuAn Unusual Copper(I) Indicator
Reevaluation of Copper(I) Affinity for Amyloid-ß Peptides by Competition with FerrozineuAn Unusual Copper(I) Indicator
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DOI：
10.1002/chem.201102746
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发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Hureau, Christelle
中科院分区：
文献类型：
--
作者：
Alies, Bruno;Badei, Bertrand;Hureau, Christelle
通过UV/Vis滴定实验测定了(5，6-diphenyl-3-(2-pyridyl)-1，2，4-triazine-4，4‘’-disulfonic酸亚铁与CuI形成发色[CuI(FZ)2]3-络合物的结合常数。其缔合常数接近1012M~(-2)，明显弱于已知的水溶CuI络合剂联苯二甲酸和2，9-二甲基-4，7-二苯基-1，10-菲咯啉二磺酸。[CuI(Fz)2]3-发色团用于UV/Vis竞争实验，以确定与阿尔茨海默病相关的淀粉样β蛋白多肽和一系列相关突变体的CuI结合亲和力。结合常数约为107M-1；这比报道的二硫苏糖醇的结合常数弱得多，证实了咪唑是比硫醇更硬的配体。每个His突变(H6A、H13A和H14A)都会影响CUI的多肽亲和力。天然的人淀粉样β蛋白被发现是一个比小鼠肽强四倍的Cui配体，后者与人的不同于三个点突变(R5G，Y10F和H13R)。
The association constant of ferrozine (5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine-4,4''-disulfonic acid) with CuI to form the chromophoric [CuI(Fz)2]3- complex was determined by UV/Vis titration experiments in Hepes buffer (0.1?m, pH 7.4). An association constant close to 1012 M-2, which is significantly weaker than those of the well-known, water-soluble, CuI chelators bicinchoninic acid and 2,9-dimethyl-4,7-diphenyl-1,10-phenantroline disulfonic acid, was found. The [CuI(Fz)2]3- chromophore was used in UV/Vis competition experiments to determine CuI binding affinity for the amyloid-beta peptide involved in Alzheimers disease and for a series of pertinent mutants. An association constant of approximately 107 M-1 was found; this is much weaker than that reported for dithiothreitol and confirms that imidazoles are harder ligands than thiolates. Each His mutation (H6A, H13A, and H14A) impacts the peptide affinity for CuI. The native human amyloid-beta peptide was found to be a fourfold-stronger CuI ligand than the murine peptide, which differs by three point mutations (R5G, Y10F, and H13R) from the human one.