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PEGylation increases antitumoral activity of arginine deiminase of Streptococcus pyogenes.
- Source :
-
Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2022 Jan; Vol. 106 (1), pp. 261-271. Date of Electronic Publication: 2021 Dec 15. - Publication Year :
- 2022
-
Abstract
- Arginine auxotrophy is a metabolic defect that renders tumor cells vulnerable towards arginine-depleting substances, such as arginine deiminase (ADI) from Streptococcus pyogenes (SpyADI). Previously, we confirmed SpyADI susceptibility on patient-derived glioblastoma multiforme (GBM) models in vitro and in vivo. For application in patients, serum half-life of the enzyme has to be increased and immunogenicity needs to be reduced. For this purpose, we conjugated the S. pyogenes-derived SpyADI with 20 kDa polyethylene glycol (PEG20) moieties, achieving a PEGylation of seven to eight of the 26 accessible primary amines of the SpyADI. The PEGylation reduced the overall activity of the enzyme by about 50% without affecting the Michaelis constant for arginine. PEGylation did not increase serum stability of SpyADI in vitro, but led to a longer-lasting reduction of plasma arginine levels in mice. Furthermore, SpyADI-PEG20 showed a higher antitumoral capacity towards GBM cells in vitro than the native enzyme. KEY POINTS: • PEGylation has no effect on the affinity of SpyADI for arginine • PEGylation increases the antitumoral effects of SpyADI on GBM in vitro • PEGylation prolongs plasma arginine depletion by SpyADI in mice.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Arginine
Humans
Hydrolases
Mice
Glioblastoma
Streptococcus pyogenes
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0614
- Volume :
- 106
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Applied microbiology and biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 34910240
- Full Text :
- https://doi.org/10.1007/s00253-021-11728-7