将婴儿利什曼原虫的铁超氧化物歧化酶作为寻找利什曼病治疗药物的目标。

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Juan Carlos García-Soriano, Héctor de Lucio, Daniel Elvira-Blázquez, Mercedes Alcón-Calderón, Natalia Sanz Del Olmo, Pedro A Sánchez-Murcia, Paula Ortega, Francisco Javier de la Mata, Antonio Jiménez-Ruiz
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引用次数: 0

摘要

利什曼原虫属和锥虫属是相关寄生虫病的病原体。要在宿主体内生存,就必须有强大的抗氧化酶机制。在锥虫中已描述了四种铁超氧化物歧化酶(FeSODA、FeSODB1、FeSODB2 和 FeSODC),它们有可能成为治疗目标。然而,利用这些纯化酶进行的研究还很少。此外,FeSODC 在利什曼原虫中仍未定性。在这项工作中,我们首次描述了重组的四种利什曼原虫 FeSOD 同工酶的纯化和酶活性,并建立了开发抑制剂的改进策略。我们提出了一个新的参数[(V*cyt. c - Vcyt. c)/Vcyt. c],与经典的细胞色素 c 还原测定中使用的参数不同,该参数与酶浓度呈线性相关。作为概念验证,我们确定了两种钌碳硅烷金属二聚体对这些异构体的 IC50 值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The repertoire of iron superoxide dismutases from Leishmania infantum as targets in the search for therapeutic agents against leishmaniasis.

Species of Leishmania and Trypanosoma genera are the causative agents of relevant parasitic diseases. Survival inside their hosts requires the existence of a potent antioxidant enzymatic machinery. Four iron superoxide dismutases have been described in trypanosomatids (FeSODA, FeSODB1, FeSODB2, and FeSODC) that hold a potential as therapeutic targets. Nonetheless, very few studies have been developed that make use of the purified enzymes. Moreover, FeSODC remains uncharacterised in Leishmania. In this work, for the first time, we describe the purification and enzymatic activity of recombinant versions of the four Leishmania FeSOD isoforms and establish an improved strategy for developing inhibitors. We propose a novel parameter [(V*cyt. c - Vcyt. c)/Vcyt. c] which, in contrast to that used in the classical cytochrome c reduction assay, correlates linearly with enzyme concentration. As a proof of concept, we determine the IC50 values of two ruthenium carbosilane metallodendrimers against these isoforms.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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