title: The Modified Heparin-Binding L-Asparaginase of Wolinella succinogenes.
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.
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: E P
authors.initials: EP
authors.lastname: Sannikova
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: N V
authors.initials: NV
authors.lastname: Bulushova
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: S E
authors.initials: SE
authors.lastname: Cheperegin
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: I I
authors.initials: II
authors.lastname: Gubaydullin
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: G G
authors.initials: GG
authors.lastname: Chestukhina
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: V V
authors.initials: VV
authors.lastname: Ryabichenko
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: I A
authors.initials: IA
authors.lastname: Zalunin
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: E K
authors.initials: EK
authors.lastname: Kotlova
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: G E
authors.initials: GE
authors.lastname: Konstantinova
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: T S
authors.initials: TS
authors.lastname: Kubasova
authors.affiliation: N. N. Blokhin Russian Cancer Research Center, Kashirskoye Shosse 24, Moscow, Russia, 115478.
authors.forename: A A
authors.initials: AA
authors.lastname: Shtil
authors.affiliation: N. N. Blokhin Russian Cancer Research Center, Kashirskoye Shosse 24, Moscow, Russia, 115478.
authors.forename: V S
authors.initials: VS
authors.lastname: Pokrovsky
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: S V
authors.initials: SV
authors.lastname: Yarotsky
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545.
authors.forename: B D
authors.initials: BD
authors.lastname: Efremov
authors.affiliation: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia, 117545. dg_kozlov@genetika.ru.
authors.forename: D G
authors.initials: DG
authors.lastname: Kozlov
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001215:Asparaginase / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007940:Leukemia L5178 / Q000188:drug therapy*; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016968:Wolinella / Q000201:enzymology* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D006493:Heparin; D001215:Asparaginase
keywords: Anti-tumor activity; Heparin-binding; L-Asparaginase; Reduced glutaminase activity; Trypsinolysis resistance; Wolinella succinogenes