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L-天冬酰胺酶作为急性淋巴细胞白血病治疗药物的结构、副作用及活性测定概述

Overview of the structure, side effects, and activity assays of l-asparaginase as a therapy drug of acute lymphoblastic leukemia.

作者信息

Wang Nanxiang, Ji Wenhui, Wang Lan, Wu Wanxia, Zhang Wei, Wu Qiong, Du Wei, Bai Hua, Peng Bo, Ma Bo, Li Lin

机构信息

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University Nanjing 211800 China

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University Xi'an 710072 China.

出版信息

RSC Med Chem. 2022 Jan 12;13(2):117-128. doi: 10.1039/d1md00344e. eCollection 2022 Feb 23.

Abstract

l-Asparaginase (l-ASNase is the abbreviation, l-asparagine aminohydrolase, E.C.3.5.1.1) is an enzyme that is clinically employed as an antitumor agent for the treatment of acute lymphoblastic leukemia (ALL). Although l-ASNase is known to deplete l-asparagine (l-Asn), causing cytotoxicity in leukemia cells, the specific molecular signaling pathways are not well defined. Because of the deficiencies in the production and administration of current formulations, the l-ASNase agent in clinical use is still associated with serious side effects, so controlling its dose and activity monitoring during therapy is crucial for improving the treatment success rate. Accordingly, it is urgent to summarize and develop effective analytical methods to detect l-ASNase activity in treatment. However, current reports on these detection methods are fragmented and also have not been systematically summarized and classified, thereby not only delaying the investigations of specific molecular mechanisms, but also hindering the development of novel detection methods. Herein, in this review, we provided a detailed summary of the l-ASNase structures, antitumor mechanism and side effects, and current detection approaches, such as fluorescence assays, colorimetric assays, spectroscopic assays and some other assays. All of them possess unique advantages and disadvantages, so it has been difficult to establish clear criteria for clinical application. We hope that this review will be of some value in promoting the development of l-ASNase activity detection methods.

摘要

L-天冬酰胺酶(L-ASNase为其缩写,即L-天冬酰胺氨基水解酶,酶学委员会编号为3.5.1.1)是一种临床上用作抗肿瘤药物来治疗急性淋巴细胞白血病(ALL)的酶。尽管已知L-ASNase会消耗L-天冬酰胺(L-Asn),从而在白血病细胞中产生细胞毒性,但具体的分子信号通路尚未明确界定。由于当前制剂在生产和给药方面存在不足,临床使用的L-ASNase制剂仍伴有严重的副作用,因此在治疗过程中控制其剂量和活性监测对于提高治疗成功率至关重要。因此,迫切需要总结并开发有效的分析方法来检测治疗过程中的L-ASNase活性。然而,目前关于这些检测方法的报道较为零散,也未得到系统的总结和分类,这不仅延误了对具体分子机制的研究,也阻碍了新型检测方法的开发。在此综述中,我们详细总结了L-ASNase的结构、抗肿瘤机制和副作用,以及当前的检测方法,如荧光测定法、比色测定法、光谱测定法和其他一些测定法。它们都有独特的优缺点,因此很难为临床应用建立明确的标准。我们希望这篇综述对促进L-ASNase活性检测方法的发展具有一定价值。

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