Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials (LSRE-LCM), Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua do Dr. Roberto Frias, 4200-465 Porto, Portugal.
Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal.
Molecules. 2020 Dec 10;25(24):5827. doi: 10.3390/molecules25245827.
l-asparaginase (ASNase, EC 3.5.1.1) is an aminohydrolase enzyme with important uses in the therapeutic/pharmaceutical and food industries. Its main applications are as an anticancer drug, mostly for acute lymphoblastic leukaemia (ALL) treatment, and in acrylamide reduction when starch-rich foods are cooked at temperatures above 100 °C. Its use as a biosensor for asparagine in both industries has also been reported. However, there are certain challenges associated with ASNase applications. Depending on the ASNase source, the major challenges of its pharmaceutical application are the hypersensitivity reactions that it causes in ALL patients and its short half-life and fast plasma clearance in the blood system by native proteases. In addition, ASNase is generally unstable and it is a thermolabile enzyme, which also hinders its application in the food sector. These drawbacks have been overcome by the ASNase confinement in different (nano)materials through distinct techniques, such as physical adsorption, covalent attachment and entrapment. Overall, this review describes the most recent strategies reported for ASNase confinement in numerous (nano)materials, highlighting its improved properties, especially specificity, half-life enhancement and thermal and operational stability improvement, allowing its reuse, increased proteolysis resistance and immunogenicity elimination. The most recent applications of confined ASNase in nanomaterials are reviewed for the first time, simultaneously providing prospects in the described fields of application.
天冬酰胺酶(ASNase,EC 3.5.1.1)是一种氨基水解酶,在治疗/制药和食品工业中有重要用途。其主要应用是作为抗癌药物,主要用于治疗急性淋巴细胞白血病(ALL),以及在淀粉丰富的食物在 100°C 以上烹饪时降低丙烯酰胺含量。也有报道称其可作为两种工业中天冬酰胺的生物传感器。然而,ASNase 的应用存在一些挑战。根据 ASNase 的来源,其在制药方面的主要挑战是它在 ALL 患者中引起的过敏反应,以及其在血液系统中的半衰期短和天然蛋白酶快速血浆清除。此外,ASNase 通常不稳定,是一种热敏酶,这也阻碍了它在食品领域的应用。通过不同的技术(如物理吸附、共价附着和包埋)将 ASNase 限制在不同的(纳米)材料中,可以克服这些缺点。总的来说,本文综述了最近报道的将 ASNase 限制在多种(纳米)材料中的策略,突出了其改进的特性,特别是特异性、半衰期延长以及热稳定性和操作稳定性的提高,允许其重复使用、提高抗蛋白水解能力和消除免疫原性。首次综述了受限 ASNase 在纳米材料中的最新应用,同时提供了所描述应用领域的前景。