PEG-Chitosan and Glycol-Chitosan for Improvement of Biopharmaceutical Propertiesof Recombinant L-Asparaginase from Erwinia carotovoraстатья
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Дата последнего поиска статьи во внешних источниках: 2 апреля 2015 г.
Аннотация:Conjugation with the new branched copolymers, PEGchitosan and glycolchitosan, is suggested to improve the
therapeutic properties of Lasparaginase 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 36 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. ChitoPEGylation, 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 PEGchitosan copolymer composition as well as composition of copoly
mer–enzyme conjugates. The proposed analytic method is “reagentfree” 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.