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
Hauptverfasser: Fonseca, Marcela Helena Gambim, Fiúza, Tayná da Silva, Morais, Stephanie Bath de, Souza, Tatiana de Arruda Campos Brasil de, Trevizani, Raphael
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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. [Display omitted] •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.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2021.111616