In Silico Design of a Chimeric Humanized L-asparaginase
| Primer Autor |
Farias, Jorge G. G.
|
| Co-autores |
Pedroso, Alejandro
Herrera Belen, Lisandra
Beltran, Jorge F. F.
Castillo, Rodrigo L. L.
Pessoa, Adalberto
Pedroso, Enrique
|
| Título |
In Silico Design of a Chimeric Humanized L-asparaginase
|
| Editorial |
MDPI
|
| Revista |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
|
| Lenguaje |
en
|
| Resumen |
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 undermine 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.
|
| Fecha Publicación |
2023
|
| Tipo de Recurso |
artículo original
|
| doi |
10.3390/ijms24087550
|
| Formato Recurso |
PDF
|
| Palabras Claves |
L-asparaginase
chimeric
silico
immunogenicity
acute lymphoblastic leukemia
|
| Ubicación del archivo | |
| Categoría OCDE |
Bioquímica y biología molecular
Química
|
| Materias |
L-asparaginasa
quimérico
silicio
inmunogenicidad
leucemia linfoblástica aguda
|
| Identificador del recurso (Mandatado-único) |
artículo original
|
| Versión del recurso (Recomendado-único) |
versión publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Id de Web of Science |
WOS:000977777600001
|
| Tipo de ruta |
verde# dorado
|
| Categoría WOS |
Bioquímica y biología molecular
Química
|
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