Article
Circumventing the side effects of L-asparaginase
Registro en:
FONSECA, Marcela Helena Gambim et al. Circumventing the side effects of L-asparaginase. Biomedicine & Pharmacotherapy, n. 139, p. 1–7, 2021.
0753-3322
Autor
Fonseca, Marcela Helena Gambim
Fiúza, Tayná da Silva
Morais, Stephanie Bath de
Souza, Tatiana de Arruda Campos Brasil de
Trevizani, Raphael
Resumen
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.