Bis(amino acidato)copper(II) compounds in blood plasma: a review of computed structural properties and amino acid affinities for Cu2+ informing further pharmacological research.

IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Jasmina Sabolović
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引用次数: 0

Abstract

Neutral bis(amino acidato)copper(II) [Cu(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa)2, two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa)2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa)2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa)2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa)2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling.

血浆中的双(氨基酸)铜(II)化合物:计算结构特性和氨基酸对 Cu2+ 的亲和力综述,为进一步的药理学研究提供信息。
中性双(氨基酸)铜(II)[Cu(aa)2]配位化合物是血浆中铜(II)氨基酸化合物的生理种类,其形式为双(l-组氨酸)铜(II)和混合三元铜(II)-l-组氨酸络合物,最好与 l-谷氨酰胺、l-苏氨酸、l-天冬酰胺和 l-半胱氨酸混合。这些氨基酸具有三种可与金属离子结合的官能团:常见的 α-氨基和羧基以及侧链极性基团。在 Cu(aa)2 中,每个氨基酸有两个配位基团在平面内与铜(II)结合,而第三个基团可以在顶端结合,这就产生了轴键和平面键的多种可能性,即双叉结合和三叉结合。迄今为止,对溶液中生理性 Cu(aa)2 化合物的实验研究尚未明确其完整的几何结构。本文简要回顾了我的研究小组利用密度泛函理论(DFT)计算生理性 Cu(aa)2 的结构特性,以找到可在水溶液中共存的低能构象。这些 DFT 研究揭示了三元 Cu(aa)2 化合物在三叉或双叉螯合时的高度构象灵活性,这可以解释血浆中的铜(II)交换反应,并为开发具有多个可能的铜(II)结合基团的小型多功能铜(II)结合药物提供信息。此外,我们对水溶液中五种生理性 Cu(aa)2 具有不同配位模式的低能构象中 Cu2+ 与氨基酸配体结合的金属离子亲和力的预测,支持了通过化学标示建模获得的它们在人体血浆中的丰度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology
Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH-TOXICOLOGY
CiteScore
3.50
自引率
4.80%
发文量
26
审稿时长
6-12 weeks
期刊介绍: Archives of Industrial Hygiene and Toxicology (abbr. Arh Hig Rada Toksikol) is a peer-reviewed biomedical scientific quarterly that publishes contributions relevant to all aspects of environmental and occupational health and toxicology.
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