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Kinetics characterization of a low immunogenic recombinant l-asparaginase from Phaseolus vulgaris with cytotoxic activity against leukemia cells.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2024 Aug; Vol. 275 (Pt 2), pp. 133731. Date of Electronic Publication: 2024 Jul 08. - Publication Year :
- 2024
-
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 K <subscript>m</subscript> and V <subscript>max</subscript> 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.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bruno Anderson Matias da Rocha reports financial support was provided by National Council for Scientific and Technological Development. Bruno Anderson Matias da Rocha reports financial support was provided by Coordination of Higher Education Personnel Improvement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Kinetics
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Cell Line, Tumor
Leukemia drug therapy
K562 Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Biofilms drug effects
Hydrogen-Ion Concentration
Temperature
Asparaginase chemistry
Asparaginase pharmacology
Asparaginase genetics
Asparaginase immunology
Phaseolus chemistry
Recombinant Proteins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 275
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 38986978
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2024.133731