L-asparaginase – A promising biocatalyst for industrial and clinical applications

Shakambari, Ganeshan; Ashokkumar, Balasubramaniem; Varalakshmi, Perumal

doi:10.1016/j.bcab.2018.11.018

Cited by 37 publications

(33 citation statements)

References 99 publications

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“…The PyCurOAc has been investigated for in vitro AGE inhibitory activity by BSA glycation assay . The fluorescence intensity (425 nm) was lesser in the BSA‐glucose system treated with the compounds than the untreated one.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of a Water‐Soluble Pyrazole Curcumin Derivative: In Vitro and In Vivo AGE Inhibitory Activity and Its Mechanism

et al. 2017

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The new chemical entity, water‐soluble pyrazole curcumin derivative (PyCurOAc) was designed, synthesized and characterized for the purpose of inhibition of AGE formation. The compound showed an excellent in vitro AGEs inhibition activity than curcumin itself as well as the standard. Further, the AGE inhibition activity was substantiated in vivo using C.elegans as an animal model. The mechanistic investigation for the inhibition of AGEs with PyCurOAc was studied with glod‐4 expressions in C.elegans and glucose trapping method. This study suggests that the synthesized compound could be used to treat the formation of AGEs in hyperglycemic nematodes and higher animals.

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Section: Resultsmentioning

confidence: 99%

“…Hence it was hypothesized that PyCurOAc may possess DPPH radical scavenging activity, hydrogen peroxide scavenger activity, and protein denaturation activity. Thus the PyCurOAc was further tested in vitro antioxidant and protein denaturation studies …”

Section: Resultsmentioning

confidence: 99%

Synthesis of a Water‐Soluble Pyrazole Curcumin Derivative: In Vitro and In Vivo AGE Inhibitory Activity and Its Mechanism

et al. 2017

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“…In contrast to healthy cells, which express L-asparagine synthetase, cancer cells, mostly of lymphoid origin, rely on exogenous L-asparagine supply from blood serum for their metabolic needs such as quick and malignant growth, spread and survival, since they are auxotrophs for L-asparagine [50,155]. Therefore, asparagine hydrolysation by ASNase from blood serum leads to p53-dependent apoptosis of cancer cells, while healthy cells remain unaffected (Figure 7) [50,155,156]. In contrast to healthy cells, which express l-asparagine synthetase, cancer cells, mostly of lymphoid origin, rely on exogenous l-asparagine supply from blood serum for their metabolic needs such as quick and malignant growth, spread and survival, since they are auxotrophs for l-asparagine [50,155].…”

Section: Therapeutic Applicationsmentioning

confidence: 99%

“…Therefore, asparagine hydrolysation by ASNase from blood serum leads to p53-dependent apoptosis of cancer cells, while healthy cells remain unaffected (Figure 7) [50,155,156]. In contrast to healthy cells, which express l-asparagine synthetase, cancer cells, mostly of lymphoid origin, rely on exogenous l-asparagine supply from blood serum for their metabolic needs such as quick and malignant growth, spread and survival, since they are auxotrophs for l-asparagine [50,155]. Therefore, asparagine hydrolysation by ASNase from blood serum leads to p53-dependent apoptosis of cancer cells, while healthy cells remain unaffected (Figure 7) [50,155,156].…”

Section: Therapeutic Applicationsmentioning

confidence: 99%

Recent Strategies and Applications for l-Asparaginase Confinement

et al. 2020

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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.

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“…[19] High-yield CFPS production of ASNase also facilitates protein engineering of ASNase. While ASNase can be expressed in fermented whole cells, conservative expression techniques and extensive purification [20,21] limit discovery and development. In contrast, CFPS features an open reaction environment which facilitates dynamic optimization of critical components, [9,22,23] monitoring of reaction progress, [24,25] and simplified purification.…”

Section: Introductionmentioning

confidence: 99%

Engineering Cell‐Free Protein Synthesis for High‐Yield Production and Human Serum Activity Assessment of Asparaginase: Toward On‐Demand Treatment of Acute Lymphoblastic Leukemia

Hunt

Wilding

Barnett

et al. 2020

Biotechnology Journal

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Acute lymphocytic leukemia (ALL) is a common childhood cancer in the United States, with over 6000 new cases diagnosed each year. Administration of bacterial asparaginase (ASNase) has improved survival rates to nearly 80%, however these therapeutics have high incidence of immunological neutralization and serum activity must be monitored for most effective treatment regimens. Here, a 72% improvement in cell‐free protein synthesis (CFPS) of FDA approved l‐asparaginase (crisantaspase) is demonstrated by employing an aspartate‐fed‐batch reactor format. A CFPS‐based ASNase activity assay as a tool for therapeutic regimentation and production quality control is also presented. This work suggests that shelf‐stable and low‐cost Escherichia coli‐based CFPS reactions may be employed on‐demand to 1) synthesize biologics on‐site for patient administration, 2) verify biologic activity for dosage calculations, and 3) monitor therapeutic activity in human serum during the treatment regimen. The combination of both therapeutic production and activity assessment introduces a concept of synergistic utility for bacterial cell lysates in modern medical treatment. Indeed, recent work with CFPS biosensors supports a not‐too‐distant future when shelf‐stable E. coli CFPS systems are used to diagnose, treat, and monitor treatment of diseases in the clinical setting.

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L-asparaginase – A promising biocatalyst for industrial and clinical applications

Cited by 37 publications

References 99 publications

Synthesis of a Water‐Soluble Pyrazole Curcumin Derivative: In Vitro and In Vivo AGE Inhibitory Activity and Its Mechanism

Synthesis of a Water‐Soluble Pyrazole Curcumin Derivative: In Vitro and In Vivo AGE Inhibitory Activity and Its Mechanism

Recent Strategies and Applications for l-Asparaginase Confinement

Engineering Cell‐Free Protein Synthesis for High‐Yield Production and Human Serum Activity Assessment of Asparaginase: Toward On‐Demand Treatment of Acute Lymphoblastic Leukemia

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