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Site-Specific POxylation of Interleukin-4

Title data

Lühmann, Tessa ; Schmidt, Marcel ; Leiske, Meike N. ; Spieler, Valerie ; Majdanski, Tobias C. ; Grube, Mandy ; Hartlieb, Matthias ; Nischang, Ivo ; Schubert, Stephanie ; Schubert, Ulrich S. ; Meinel, Lorenz:
Site-Specific POxylation of Interleukin-4.
In: ACS Biomaterials Science & Engineering. Vol. 3 (2017) Issue 3 . - pp. 304-312.
ISSN 2373-9878
DOI: https://doi.org/10.1021/acsbiomaterials.6b00578

Official URL: Volltext

Abstract in another language

Polymer conjugated biologics form a multibillion dollar market, dominated by poly(ethylene glycol) (PEG). Recent reports linked PEGs to immunological concerns, fueling the need for alternative polymers. Therefore, we are presenting a strategy replacing PEG by poly(2-oxazoline) (POx) polymers using genetically engineered interleukin-4 (IL-4) featuring an unnatural amino acid for site-specific conjugation through bioorthogonal copper-catalyzed azide alkyne cycloaddition (CuAAC). Conjugation yields of IL-4-PEG were poor and did not respond to an increase in the copper catalyst. In contrast, POxylated IL-4 conjugates resulted in homogeneous conjugate outcome, as demonstrated electrophoretically by size exclusion chromatography and analytical ultracentrifugation. Furthermore, POxylation did not impair thermal and chemical stability, and preserved wild-type IL-4 activity for the conjugates as demonstrated by TF-1 cell proliferation and STAT-6 phosphorylation in HEK293T cells, respectively. In conclusion, POxylation provides an interesting alternative to PEGylation with superior outcome for the synthesis yield by CuAAC and resulting in conjugates with excellent thermal and chemical stress profiles as well as biological performances.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: cytokine engineering; 2-methyl-2-oxazoline; genetic code expansion; CuAAC (copper(I) catalyzed azide alkyne cycloaddition); bioconjugation
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Junior Professor Sustainable and Functional Polymer Systems > Junior Professor Sustainable and Functional Polymer Systems - Juniorprof. Dr. Meike Leiske
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Junior Professor Sustainable and Functional Polymer Systems
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 18 Jan 2023 14:44
Last Modified: 13 Mar 2023 08:44
URI: https://eref.uni-bayreuth.de/id/eprint/73449