Circumventing the side effects of L-asparaginase

Biomedicine & Pharmacotherapy

Tayná da Silva Fiúza¹  Raphael Trevizani²  Marcela Helena Gambim Fonseca²  Stephanie Bath de Morais³  Tatiana de Arruda Campos Brasil de Souza³ 

[1]Bioinformatics Multidisciplinary Environment, BioME, Natal, RN 59078-400, Brazil

[2]Fundação Oswaldo Cruz, Fiocruz-Ceará, Eusébio, CE 61760-000, Brazil

[3]Fundação Oswaldo Cruz, Instituto Carlos Chagas, Curitiba, PR 81350010, Brazil

关键词: Immunogenicity;    L-glutaminase activity;    Half-life;    Epitope prediction;    Deimmunization;    Protein engineering;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown