title: [Bacterial recombinant L-asparaginases: properties, structure and anti-proliferative activity].
abstract: For more than 40 years L-asparaginases are used in combined therapy of acute lymphoblastic leukemia in children and the range of tumors sensitive to these enzymes constantly extends. This review summarizes results of studies aimed at creation of new systems for heterological expression of bacterial L-asparaginases as Erwinia carotovora (EwA), Helicobacter pylori (HpA), Yersinia pseudotuberculosis (YpA) and Rhodospirillum rubrum (RrA); special attention is paid to isolation of purified enzymes and their crystallization, modification by chitosan/polyethylene, physicochemical, kinetic and structural properties characterization, and the study of the cytotoxic or anti-proliferative activity of new recombinant L-asparaginases on cell cultures in vitro. The resultant recombinant L-asparaginases (EwA, YpA, HpA и RrA) exhibit reasonable cytotoxic action on the human leukemia cells comparable to the pharmacologically available L-asparaginase EcA and represent practical interest in respect to creation, on their basis, new effective antineoplastic remedies. Further prospects of researches on bacterial L-asparaginases are associated with development of analogs of Rhodospirillum rubrum L-asparaginase (RrA) by means of directed changes of the protein structure using genetic engineering, development of chito-PEGylation for receiving L-asparaginase preparations with improved pharmacokinetic characteristics.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Sokolov
authors.affiliation: Centre "Bioengineering", Russian Academy of Sciences, Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Eldarov
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Pokrovskaya
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: S S
authors.initials: SS
authors.lastname: Aleksandrova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: O Yu
authors.initials: OY
authors.lastname: Abakumova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Podobed
authors.affiliation: Lomonosov Moscow State University, Chemical Faculty, Moscow, Russia.
authors.forename: N S
authors.initials: NS
authors.lastname: Melik-Nubarov
authors.affiliation: Lomonosov Moscow State University, Chemical Faculty, Moscow, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Kudryashova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Grishin
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A I
authors.initials: AI
authors.lastname: Archakov
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001215:Asparaginase / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D016480:Helicobacter pylori / Q000201:enzymology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D008969:Molecular Sequence Data; D016973:Pectobacterium carotovorum / Q000201:enzymology; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D012247:Rhodospirillum rubrum / Q000201:enzymology; D015011:Yersinia pseudotuberculosis / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D001215:Asparaginase
keywords: L-asparaginase; L-glutaminase; PEGylated L-asparaginase; chito-PEGylation; leukemia; recombinant proteins