Hejnaes K R, Sehested B, Worsaae H, Mølvig J, Wollmer A
Novo-Nordisk A/S, Gentofte, Denmark.
Biol Chem Hoppe Seyler. 1990 Jan;371(1):23-30. doi: 10.1515/bchm3.1990.371.1.23.
Interleukin-1 beta (IL-1 beta) and N-terminally extended Met-Glu-Ala-Glu-IL-1 beta (MEAE-IL-1 beta) were cloned and expressed in E. coli. Extension of the chain results in a limited conformational change reflected by the CD spectrum in the far ultraviolet, while the aromatic side chains responsible for the CD in the near ultraviolet are not affected. No difference in immunoreactivity between IL-1 beta and MEAE-IL-1 beta is observed in the IL-1 beta ELISA. Like IL-1 beta, MEAE-IL-1 beta exhibits biological activity tested in the costimulatory mouse thymocyte (LAF) assay. The specific biological activity of IL-1 beta is 3 x 10(8) U/mg and that of MEAE-IL-1 beta 3 x 10(6) U/mg. Like IL-1 beta, MEAE-IL-1 beta displaces [125I]IL-1 beta from mouse thymocytes and the binding affinities of the two forms differ by a factor of 10(2). Finally the inhibitory effect of the two IL-1 beta forms on in vitro insulin secretion from isolated rat islets of Langerhans was measured. Again MEAE-IL-1 beta is 10(2) times less potent than IL-1 beta. The structure-activity relationship for IL-1 beta and MEAE-IL-1 beta is discussed.
白细胞介素-1β（IL-1β）和N端延伸的Met-Glu-Ala-Glu-IL-1β（MEAE-IL-1β）在大肠杆菌中克隆并表达。链的延伸导致远紫外区CD光谱反映出有限的构象变化，而近紫外区负责CD的芳香族侧链不受影响。在IL-1β ELISA中未观察到IL-1β和MEAE-IL-1β之间免疫反应性的差异。与IL-1β一样，MEAE-IL-1β在共刺激小鼠胸腺细胞（LAF）试验中表现出生物活性。IL-1β的比生物活性为3×10⁸ U/mg，MEAE-IL-1β为3×10⁶ U/mg。与IL-1β一样，MEAE-IL-1β从小鼠胸腺细胞中置换出[¹²⁵I]IL-1β，两种形式的结合亲和力相差10²倍。最后测量了两种IL-1β形式对离体大鼠胰岛体外胰岛素分泌的抑制作用。同样，MEAE-IL-1β的效力比IL-1β低10²倍。讨论了IL-1β和MEAE-IL-1β的构效关系。
