Bacterial recombinant L-asparaginases: properties, structure and anti-proliferative activity


1. Institute of Biomedical Chemistry, Moscow, Russia
2. Centre “Bioengineering”, Russian Academy of Sciences, Moscow, Russia
3. Lomonosov Moscow State University, Chemical Faculty, Moscow, Russia
Type: Review
DOI: 10.18097/PBMC20156103312      UDK: 612.015.      PubMed Id: 26215408
Year: 2015 vol: 61  issue:3  pages: 312-324
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.
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Reference: Sokolov N.N., Eldarov M.A., Pokrovskaya M.V., Aleksandrova S.S., Abakumova O.Yu., Podobed O.V., Melik-Nubarov N.S., Kudryashova E.V., Grishin D.V., Archakov A.I., Bacterial recombinant L-asparaginases: properties, structure and anti-proliferative activity, Biomeditsinskaya khimiya, 2015, vol: 61(3), 312-324.
This paper is also available as the English translation:10.1134/S199075081504006X
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