Chemo-Enzymatic PEGylation/POxylation of Murine Interleukin‑4
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Haas, Dorothee; Hauptstein, Niklas; Dirauf, Michael; Driessen, Marc D.; Ruopp, Matthias; Schubert, Ulrich S.; Lühmann, Tessa; Meinel, Lorenz
- Abstract:
- Interleukin-4 (IL-4) is a potentially interesting anti-
inflammatory therapeutic, which is rapidly excreted. Therefore,
serum half-life extension by polymer conjugation is desirable,
which may be done by PEGylation. Here, we use PEtOx as an
alternative to PEG for bioconjugate engineering. We genetically
extended murine IL-4 (mIL-4) with the D -domain of insulin-like
growth factor I (IGF-I), a previously identified substrate of
transglutaminase (TG) Factor XIIIa (FXIIIa). Thereby, engi-
neered mIL-4 (mIL-4-TG) became an educt for TG catalyzed C-
terminal, site-directed conjugation. This was deployed to enzymati-
cally couple an azide group containing peptide sequence to mIL-4,
allowing C-terminal bioconjugation of polyethylene glycol or
poly(2-ethyl-2-oxazoline). Both bioconjugates had wild-type
potency and alternatively polarized macrophages.
- Research areas:
- Year:
- 2022
- Type of Publication:
- Article
- Journal:
- Bioconjugate Chemistry
- Volume:
- 33
- Pages:
- 97 - 104
- DOI:
- https://doi.org/10.1021/acs.bioconjchem.1c00495