| Literature DB >> 27198565 |
E P Sannikova1, N V Bulushova1, S E Cheperegin1, I I Gubaydullin1, G G Chestukhina1, V V Ryabichenko1, I A Zalunin1, E K Kotlova1, G E Konstantinova1, T S Kubasova1, A A Shtil2, V S Pokrovsky2, S V Yarotsky1, B D Efremov1, D G Kozlov3.
Abstract
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.Entities:
Keywords: Anti-tumor activity; Heparin-binding; L-Asparaginase; Reduced glutaminase activity; Trypsinolysis resistance; Wolinella succinogenes
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Year: 2016 PMID： 27198565 DOI： 10.1007/s12033-016-9950-1
Source DB: PubMed Journal: Mol Biotechnol ISSN： 1073-6085 Impact factor: 2.695