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Nonclinical Evaluation of Single-Mutant Asparaginases Obtained by Double-Mutant Deconvolution: Improving Toxicological, Immune and Inflammatory Responses

Int J Mol Sci. 2024-05; 
Grace Ruiz-Lara, Tales A Costa-Silva, Jorge Javier Muso-Cachumba, Johanna Cevallos Espinel, Marina Gabriel Fontes, Mitla Garcia-Maya, Khondaker Miraz Rahman, Carlota de Oliveira Rangel-Yagui, Gisele Monteiro
Products/Services Used Details Operation
Codon Optimization … coli asparaginase type II enzyme (WT), encoded by ansB gene (UNIPROT P00805), was synthesised with optimised codon usage by GenScript (Piscataway, NJ, USA) and used as a … Get A Quote

摘要

Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability ... More

关键词

E. coli asparaginase, bioengineer, leukaemia, nonclinical assays