Chemo-Enzymatic PEGylation/POxylation of Murine Interleukin‑4

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:

• Polymer Science

Year:

2022

Type of Publication:

Article

Journal:

Bioconjugate Chemistry

Volume:

33

Pages:

97 - 104

DOI:

https://doi.org/10.1021/acs.bioconjchem.1c00495