Abstract
In order to study the effect of glycosylation on its biological activities and to develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with C9 spacer was chemically coupled to human recombinant IL-1α. NeuAc-coupled IL-1α (NeuAc-IL-1α) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1α. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1α exhibited a marked reduction in the activity to up-regulate serum IL-6, moderate reduction in the activities to up-regulate serum amyloid A and NOx. However, it exhibited comparable activities as IL-1α to down-regulate serum glucose and to improve the recovery of peripheral white blood cells from myelosuppression in 5-fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1α was high compared to IL-1α. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.
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Sasayama, S., Moriya, K., Chiba, T. et al. Glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetylneuraminic acid exhibits selective activities in vivo and altered tissue distribution. Glycoconj J 17, 353–359 (2000). https://doi.org/10.1023/A:1007181929405
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DOI: https://doi.org/10.1023/A:1007181929405