The Modified Heparin-Binding l-Asparaginase of Wolinella succinogenes
| Autor: | E. K. Kotlova, E. P. Sannikova, Vadim S. Pokrovsky, T. S. Kubasova, I. I. Gubaydullin, G. E. Konstantinova, N. V. Bulushova, V. V. Ryabichenko, S. V. Yarotsky, I. A. Zalunin, G. G. Chestukhina, Alexander A. Shtil, B. D. Efremov, S. E. Cheperegin, D. G. Kozlov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Asparaginase Cell Survival Antineoplastic Agents Bioengineering Peptide Biology Applied Microbiology and Biotechnology Biochemistry law.invention Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bacterial Proteins law medicine Animals Humans Leukemia L5178 Molecular Biology Cell Proliferation chemistry.chemical_classification Heparin Cell growth Xenograft Model Antitumor Assays Recombinant Proteins In vitro Wolinella Amino acid 030104 developmental biology Enzyme Amino Acid Substitution chemistry 030220 oncology & carcinogenesis Recombinant DNA K562 Cells Biotechnology medicine.drug |
| Zdroj: | Molecular Biotechnology. 58:528-539 |
| ISSN: | 1559-0305 1073-6085 |
| Popis: | The modified asparaginase Was79 was derived from the recombinant wild-type L-asparaginase of Wolinella succinogenes. The Was79 contains the amino acid substitutions V23Q and K24T responsible for the resistance to trypsinolysis and the N-terminal heparin-binding peptide KRKKKGKGLGKKR responsible for the binding to heparin and tumor K562 cells in vitro. When tested on a mouse model of Fischer lymphadenosis L5178Y, therapeutic efficacy of Was79 was significantly higher than that of reference enzymes at all single therapeutic doses used (125-8000 IU/kg). At Was79 single doses of 500-8000 IU/kg, the complete remission rate of 100 % was observed. The Was79 variant can be expressed intracellularly in E. coli as a less immunogenic formyl-methionine-free form at high per cell production levels. |
| Databáze: | OpenAIRE |
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