Kinetics characterization of a low immunogenic recombinant l-asparaginase from Phaseolus vulgaris with cytotoxic activity against leukemia cells.
Int J Biol Macromol
; 275(Pt 2): 133731, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38986978
ABSTRACT
l-asparaginases play a crucial role in the treatment of acute lymphoblastic leukemia (ALL), a type of cancer that mostly affects children and teenagers. However, it is common for these molecules to cause adverse reactions during treatment. These downsides ignite the search for novel asparaginases to mitigate these problems. Thus, this work aimed to produce and characterize a recombinant asparaginase from Phaseolus vulgaris (Asp-P). In this study, Asp-P was expressed in Escherichia coli with high yields and optimum activity at 40 °C, pH 9.0. The enzyme Km and Vmax values were 7.05 mM and 1027 U/mg, respectively. Asp-P is specific for l-asparagine, showing no activity against l-glutamine and other amino acids. The enzyme showed a higher cytotoxic effect against Raji than K562 cell lines, but only at high concentrations. In silico analysis indicated that Asp-P has lower immunogenicity than a commercial enzyme. Asp-P induced biofilm formation by Candida sp. due to sublethal dose, showing an underexplored potential of asparaginases. The absence of glutaminase activity, lower immunogenicity and optimal activity similar to physiological temperature conditions are characteristics that indicate Asp-P as a potential new commercial enzyme in the treatment of ALL and its underexplored application in the treatment of other diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asparaginase
/
Proteínas Recombinantes
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Phaseolus
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda