Repositorio UFRO · Omeka S

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	http://dx.doi.org/10.3390/ijms24087550
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