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https://www.arca.fiocruz.br/handle/icict/47629
CIRCUMVENTING THE SIDE EFFECTS OF L-ASPARAGINASE
Immunologic Factors
L-glutaminase activity
Half-Life
Epitope prediction
Deimmunization
Protein Engineering
Glutaminasa
Semivida
Mapeo Epitopo
Ingeniería de Proteínas
Author
Affilliation
Fundação Oswaldo Cruz. Fiocruz Ceará. Eusébio, CE, Brasil.
Núcleo Multidisciplinar de Bioinformática. BioME, RN, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Fiocruz Ceará. Eusébio, CE, Brasil.
Núcleo Multidisciplinar de Bioinformática. BioME, RN, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Fiocruz Ceará. Eusébio, CE, Brasil.
Abstract
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.
Keywords
ImmunogenicityImmunologic Factors
L-glutaminase activity
Half-Life
Epitope prediction
Deimmunization
Protein Engineering
Keywords in Spanish
Factores InmunológicosGlutaminasa
Semivida
Mapeo Epitopo
Ingeniería de Proteínas
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