使用焦磷酸特异性受体选择性溶解二水焦磷酸钙晶体

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-11-04 Epub Date: 2024-09-09 DOI:10.1002/cbic.202400319
Zachary H Paine, Mayank Sharma, Simon H Friedman
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引用次数: 0

摘要

假性痛风是由于患者关节中沉积了高度不溶性的二水焦磷酸钙(CPPD)结晶而引起的。这会导致炎症,最终造成关节损伤。CPPD 的不溶性是由二阳离子钙离子与四阴离子焦磷酸离子之间的强大吸引力造成的。溶解 CPPD 所面临的挑战之一是,一种相关的矿物质羟基磷灰石(HA)以骨的形式大量存在,并且也含有强烈相互作用的钙离子和磷酸根离子。我们这项工作的目的是选择性地溶解 CPPD,而不是 HA。为了实现这一目标,我们使用了一种已知的焦磷酸受体,它含有两个络合锌离子,这两个锌离子的间距非常适合与焦磷酸的四阴离子相互作用。我们假设,这种分子可以充当预组织的四阳离子,能够与 CPPD 晶格中的两个钙离子竞争。我们通过肉眼观察和对释放出的磷的分析表明,这种分子能够优先溶解 CPPD,而不是与之密切相关的 HA,从而为治疗假性痛风奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Pseudo-gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di-cationic calcium ions with tetra-anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra-anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra-cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo-gout.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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