马兜铃酸在各种环糊精和血清白蛋白之间的竞争结合作为急性中毒解毒的模型

IF 2.1 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Supramolecular Chemistry Pub Date : 2021-10-03 DOI:10.1080/10610278.2022.2109472

Nika Gazdek, I. Zonjić, I. Nikšić-Franjić, Leo Leo Frkanec, I. Piantanida

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引用次数: 0

摘要

摘要研究表明，马兜铃酸毒素(ARI)及其荧光类似物可与多种环糊精(CDs)形成包合物，包括临床上常用的γ-CD: Sugammadex。ARI对CD的结合亲和力因CD大小和边缘修饰而异，其中ARI/Sugammadex复合物的稳定性比ARI与血清白蛋白(BSA)结合的稳定性高2倍，BSA是一种众所周知的小分子转运蛋白，与ARI复合物与ds-DNA相似。分子模型支持ARI/ Sugammadex配合物的形成，ARI的羧基暴露于水，而ARI凝聚的芳香部分深浸在cd腔中。这些结果证明了CDs可以作为急性急性急性中毒急性急性急性中毒的急救手段，通过结合大部分毒素与血清白蛋白或ds-DNA竞争，并显着减少机体对ARI的吸收，类似于Sugammadex从血液中提取药物以阻止其生物活性。图形抽象

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Competitive binding of aristolochic acid between various cyclodextrins and serum albumin as a model for acute poisoning detoxification

ABSTRACT We showed that aristolochic acid toxin (ARI) and its fluorescent analogue form inclusion complexes with various cyclodextrins (CDs), including the clinically used γ-CD: Sugammadex. The binding affinity of ARI towards CDs varied on a CD size and rim modifications, whereby the stability of ARI/Sugammadex complex was 2-fold greater than ARI binding to serum albumin (BSA), blood protein well-known as a transporter of small molecules and similar to the ARI complex with ds-DNA. Molecular modelling supported the formation of ARI/ Sugammadex complex with carboxyl group of ARI exposed to water and ARI-condensed aromatic moiety deeply immersed into CD-cavity. These results are a proof-of-concept that CDs could be used as a first aid upon acute intoxication with ARI by binding larger part of the toxin in competition with serum albumin or ds-DNA and significantly reducing ARI absorption in the organism, similarly as Sugammadex extracts drugs from blood to stop their bioactivity. Graphical abstract

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来源期刊

Supramolecular Chemistry 化学-化学综合

CiteScore

3.60

自引率

3.00%

发文量

审稿时长

2.7 months

期刊介绍： Supramolecular Chemistry welcomes manuscripts from the fields and sub-disciplines related to supramolecular chemistry and non-covalent interactions. From host-guest chemistry, self-assembly and systems chemistry, through materials chemistry and biochemical systems, we interpret supramolecular chemistry in the broadest possible sense. Interdisciplinary manuscripts are particularly encouraged. Manuscript types include: high priority communications; full papers; reviews, and; Methods papers, techniques tutorials highlighting procedures and technologies that are important to the field. We aim to publish papers in a timely fashion and as soon as a paper has been accepted and typeset it will be published in electronic form on the Latest articles section of the website. The two most important review criteria are that the paper presents high-quality work that fits generally into the broad spectrum of activities in the supramolecular chemistry field. Under normal circumstances, Supramolecular Chemistry does not consider manuscripts that would be more suitable in a highly specialized journal. This includes, but is not limited to, those based mostly or exclusively on topics such as solid state/X-ray structures, computational chemistry, or electrochemistry. . The two most important review criteria are that the paper presents high-quality work that fits generally into the broad spectrum of activities in the supramolecular chemistry field.