Version 1
: Received: 23 January 2023 / Approved: 30 January 2023 / Online: 30 January 2023 (03:21:51 CET)
How to cite:
Pedroso, A.; Herrera Belén, L.; Beltrán, J.F.; Castillo, R.L.; Pedroso, E.; Pessoa, A.; Farías, J.G. In Silico Design of a Chimeric Humanized L-Asparaginase.. Preprints2023, 2023010537. https://doi.org/10.20944/preprints202301.0537.v1.
Pedroso, A.; Herrera Belén, L.; Beltrán, J.F.; Castillo, R.L.; Pedroso, E.; Pessoa, A.; Farías, J.G. In Silico Design of a Chimeric Humanized L-Asparaginase.. Preprints 2023, 2023010537. https://doi.org/10.20944/preprints202301.0537.v1.
Cite as:
Pedroso, A.; Herrera Belén, L.; Beltrán, J.F.; Castillo, R.L.; Pedroso, E.; Pessoa, A.; Farías, J.G. In Silico Design of a Chimeric Humanized L-Asparaginase.. Preprints2023, 2023010537. https://doi.org/10.20944/preprints202301.0537.v1.
Pedroso, A.; Herrera Belén, L.; Beltrán, J.F.; Castillo, R.L.; Pedroso, E.; Pessoa, A.; Farías, J.G. In Silico Design of a Chimeric Humanized L-Asparaginase.. Preprints 2023, 2023010537. https://doi.org/10.20944/preprints202301.0537.v1.
Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.
Keywords
L-asparaginase; chimeric; in silico; immunogenicity; acute lymphoblastic leukemia
Subject
LIFE SCIENCES, Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
*
