Circumventing the side effects of L-asparaginase
L-asparaginase is an enzyme that catalyzes the degradation of asparagine and successfully used in the treatment of acute lymphoblastic leukemia. L-asparaginase toxicity is either related to hypersensitivity to the foreign protein or to a secondary L-glutaminase activity that causes inhibition of pro...
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Veröffentlicht in: | Biomedicine & pharmacotherapy 2021-07, Vol.139, p.111616-111616, Article 111616 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | L-asparaginase is an enzyme that catalyzes the degradation of asparagine and successfully used in the treatment of acute lymphoblastic leukemia. L-asparaginase toxicity is either related to hypersensitivity to the foreign protein or to a secondary L-glutaminase activity that causes inhibition of protein synthesis. PEGylated versions have been incorporated into the treatment protocols to reduce immunogenicity and an alternative L-asparaginase derived from Dickeya chrysanthemi is used in patients with anaphylactic reactions to the E. coli L-asparaginase. Alternative approaches commonly explore new sources of the enzyme as well as the use of protein engineering techniques to create less immunogenic, more stable variants with lower L-glutaminase activity. This article reviews the main strategies used to overcome L-asparaginase shortcomings and introduces recent tools that can be used to create therapeutic enzymes with improved features.
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•L-asparaginase is used in the treatment of acute lymphoblastic leukemia.•L-asparaginase toxicity is linked to hypersensitivity in many patients.•Current formulations have a relatively short shelf life.•Site-directed mutagenesis has been used to obtain better recombinant variables.•Alternative sources and formulations of L-asparaginase are promising alternatives. |
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ISSN: | 0753-3322 1950-6007 |
DOI: | 10.1016/j.biopha.2021.111616 |