期刊
CHEMBIOCHEM
卷 17, 期 22, 页码 2123-2128出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600480
关键词
click chemistry; CuAAC; cytokines; genetic code expansion; SPAAC; unnatural amino acids
资金
- DFG [ME 3920/3-1]
- Sino-German center
- Germany Federal Ministry of Education and Research [13N13454]
Driving macrophage (Mf) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin-4 (IL-4) promotes polarization into the M2-Mf phenotype, but its systemic use is constrained by dose-limiting toxicity. Consequently, we developed IL-4-decorated surfaces aiming at sustained and localized activity. IL-4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell-stimulation ability and binding affinity to IL4R alpha similar to those of wt-IL-4. Copper-catalyzed (CuAAC) and copper-free strain-promoted (SPAAC) 1,3-dipolar azide-alkyne cycloadditions were used to site-selectively anchor IL-4 to agarose surfaces. These surfaces had sustained IL-4 activity, as demonstrated by TF-1 cell proliferation and M2, but not M1, polarization of M-CSF-generated human M phi. The approach provides a blueprint for the engineering of cytokine-activated surfaces profiled for sustained and spatially controlled activity.
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