PEG-chitosan and glycol-chitosan for improvement of biopharmaceutical properties of recombinant L-asparaginase from Erwinia carotovora

Biochemistry. Biokhimii︠a︡
K V Sukhoverkov, E V Kudryashova

Abstract

Conjugation with the new branched copolymers, PEG-chitosan and glycol-chitosan, is suggested to improve the therapeutic properties of L-asparaginase from Erwinia carotovora (EwA). The structure and composition of such conjugates were optimized for maximal catalytic efficiency (kcat/KM) under physiological conditions, yielding improvement by a factor of 3-6 compared to the native enzyme. This effect is attributed mainly to the shift of pH activity profile towards lower pH values due to the polycationic nature of the copolymer. The thermostability of EwA conjugates was also considerably improved. Chito-PEGylation, similarly to PEGylation, can be expected to improve pharmacokinetic properties and to reduce immunogenicity of this medically relevant enzyme. It is worth mentioning that a new versatile approach based on IR spectroscopy has been developed to determine PEG-chitosan copolymer composition as well as composition of copolymer-enzyme conjugates. The proposed analytic method is "reagent-free" and allows fast and reliable determination of parameters of interest from the single IR spectrum in contrast to laborious and unreliable methods based on polymer free amino group titration with TNBS and OPA.

References

Apr 17, 2002·International Journal of Pharmaceutics·Alexandre Learth SoaresJosé Abrahão-Neto
Jan 13, 2006·The New England Journal of Medicine·Ching-Hon Pui, William E Evans
Jul 24, 2008·The FEBS Journal·Anastassios C PapageorgiouJulya Krasotkina

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Citations

Jan 31, 2016·Colloids and Surfaces. B, Biointerfaces·Irina M Deygen, Еlena V Kudryashova
Dec 18, 2015·Analytical and Bioanalytical Chemistry·Elena V Kudryashova, Kirill V Sukhoverkov
Sep 27, 2016·Expert Opinion on Drug Delivery·Chintan BhavsarAbdelwahab Omri
Jul 29, 2015·Biomedit︠s︡inskai︠a︡ khimii︠a︡·N N SokolovA I Archakov
Mar 30, 2016·Colloids and Surfaces. B, Biointerfaces·Shengli WanJingqing Zhang
May 16, 2017·Bioconjugate Chemistry·Ahmet Ulu, Burhan Ates

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