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金属-淀粉样蛋白β复合物的受体性质调谐。Ni(II)-Aβ 与磷酸盐/核苷酸相互作用的研究。

Tuning Receptor Properties of Metal-Amyloid Beta Complexes. Studies on the Interaction between Ni(II)-Aβ and Phosphates/Nucleotides.

机构信息

Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, Warsaw 00-664, Poland.

Faculty of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland.

出版信息

Inorg Chem. 2021 Dec 20;60(24):19448-19456. doi: 10.1021/acs.inorgchem.1c03285. Epub 2021 Dec 8.

DOI:10.1021/acs.inorgchem.1c03285
PMID:34878265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8693174/
Abstract

Amyloid-beta (Aβ) peptides, potentially relevant in the pathology of Alzheimer's disease, possess distinctive coordination properties, enabling an effective binding of transition-metal ions, with a preference for Cu(II). In this work, we found that a N-truncated Aβ analogue bearing a His-2 motif, Aβ, forms a stable Ni(II) high-spin octahedral complex at a physiological pH of 7.4 with labile coordination sites and facilitates ternary interactions with phosphates and nucleotides. As the pH increased above 9, a spin transition from a high-spin to a low-spin square-planar Ni(II) complex was observed. Employing electrochemical techniques, we showed that interactions between the binary Ni(II)-Aβ complex and phosphate species result in significant changes in the Ni(II) oxidation signal. Thus, the Ni(II)-Aβ complex could potentially serve as a receptor in electrochemical biosensors for phosphate species. The obtained results could also be important for nickel toxicology.

摘要

淀粉样蛋白-β(Aβ)肽在阿尔茨海默病的病理学中可能具有重要作用,其具有独特的配位性质,能够有效地与过渡金属离子结合,尤其是 Cu(II)。在这项工作中,我们发现一种带有 His-2 基序的 N 截断 Aβ类似物 Aβ,在生理 pH 值为 7.4 时形成稳定的 Ni(II)高自旋八面体配合物,具有不稳定的配位位点,并促进与磷酸盐和核苷酸的三元相互作用。当 pH 值升高到 9 以上时,观察到从高自旋到低自旋正方形平面 Ni(II)配合物的自旋转变。我们利用电化学技术表明,二元 Ni(II)-Aβ配合物与磷酸盐之间的相互作用导致 Ni(II)氧化信号发生显著变化。因此,Ni(II)-Aβ配合物可能在用于磷酸盐的电化学生物传感器中作为受体。所得结果对于镍毒理学也可能很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/7a9473c5add1/ic1c03285_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/3413220ae273/ic1c03285_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/310f9ed5eba0/ic1c03285_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/db1ce4efb882/ic1c03285_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/ecec68f9c34e/ic1c03285_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/420abee3b7ef/ic1c03285_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/5d2603cec1b7/ic1c03285_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/7a9473c5add1/ic1c03285_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/3413220ae273/ic1c03285_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/310f9ed5eba0/ic1c03285_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/db1ce4efb882/ic1c03285_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/ecec68f9c34e/ic1c03285_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/420abee3b7ef/ic1c03285_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/5d2603cec1b7/ic1c03285_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ae/8693174/7a9473c5add1/ic1c03285_0008.jpg

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本文引用的文献

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Inorg Chem. 2021 Sep 6;60(17):12772-12780. doi: 10.1021/acs.inorgchem.1c00899. Epub 2021 Aug 20.
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Copper(ii) complex of N-truncated amyloid-β peptide bearing a His-2 motif as a potential receptor for phosphate anions.带有His-2基序的N端截短淀粉样β肽的铜(II)配合物作为磷酸根阴离子的潜在受体
Dalton Trans. 2021 Feb 28;50(8):2726-2730. doi: 10.1039/d0dt03898a. Epub 2021 Feb 12.
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Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine.
设计的金属-ATCUN衍生物:与化学、生物学和医学相关的基于氧化还原和非氧化还原的应用。
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Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production.与抗菌肽相连的铜结合基序 Xxx-His 或 Xxx-Zzz-His(ATCUN):铜结合、抗菌活性和 ROS 产生。
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Aβ Peptides: N-Terminal Truncation Yields Tunable Cu(II) Complexes.β淀粉样肽:N 端截断得到可调节的 Cu(II)配合物。
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