糖基化人白细胞介素-1α，即新糖基化IL-1α，与N-乙酰神经氨酸偶联后在体内表现出选择性活性并改变了组织分布。
Glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N-acetylneuraminic acid exhibits selective activities in vivo and altered tissue distribution.
作者信息
Sasayama S, Moriya K, Chiba T, Matsumura T, Hayashi H, Hayashi A, Onozaki K
机构信息
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Japan.
出版信息
Glycoconj J. 2000 Jun;17(6):353-9. doi: 10.1023/a:1007181929405.
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-1alpha. NeuAc-coupled IL-1alpha (NeuAc-IL-1alpha) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1alpha. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1alpha 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-1alpha 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-1alpha was high compared to IL-1alpha. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.
为了研究糖基化对其生物学活性的影响并开发具有较低有害作用的白细胞介素-1（IL-1），将带有C9间隔基的N-乙酰神经氨酸（NeuAc）化学偶联到人重组IL-1α上。与IL-1α相比，NeuAc偶联的IL-1α（NeuAc-IL-1α）在体外表现出降低的活性和受体结合亲和力，降低了约十倍。在本研究中，我们检测了多种IL-1在体内的活性。NeuAc-IL-1α上调血清IL-6的活性显著降低，上调血清淀粉样蛋白A和NOx的活性中度降低。然而，在下调血清葡萄糖以及改善5-氟尿嘧啶处理小鼠骨髓抑制后外周白细胞的恢复方面，它与IL-1α表现出相当的活性。此外，与IL-1α相比，NeuAc-IL-1α的组织水平较高。这些结果表明，与NeuAc偶联使我们能够开发出在体内具有选择性活性和更高组织水平的新型IL-1。
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