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Conjugation of High-Molecular Weight Poly(ethylene glycol) to Cytokines: Granulocyte-Macrophage Colony-Stimulating Factors as Model Substrates

机译:高分子量聚乙二醇与细胞因子的缀合:粒细胞-巨噬细胞集落刺激因子作为模型基质。

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The ability of hte small receptor-binding protein, recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), to increase the abundance of certain blood cell types in mice was enhanced markedly by covalent attachment of a single long strand of PEG (30-40 kDa). Potency was not increased further by coupling a second strand. Such conjugates can be synthesized efficiently by reaction of protein amino groups with PEG propionaldehydes in the presence of NaBH_3CN or with PEG p-nitrophenyl carbonates. Both methods have been used to prepare recombinant human GM-CSF conjugates of predetermiend composition, e.g. PEG_1GM-CSF and PEG_2GM-CSF, in high yield. These compounds, or analogous derivatives of other cytokines, purified by ion-echange and size-exclusion chromatography, may be suitable candidates for pharmaceutical development.
机译:PEG长单价共价连接显着增强了小受体结合蛋白重组鼠粒细胞巨噬细胞集落刺激因子(GM-CSF)在小鼠中增加某些血细胞类型的能力。 30-40 kDa)。通过偶联第二链没有进一步提高效力。可以通过在NaBH_3CN存在下使蛋白质氨基与PEG丙醛或PEG对硝基苯基碳酸酯反应来有效合成此类偶联物。两种方法都已用于制备预定组成的重组人GM-CSF缀合物,例如。 PEG_1GM-CSF和PEG_2GM-CSF,高收率。通过离子交换色谱和尺寸排阻色谱法纯化的这些化合物或其他细胞因子的类似衍生物可能是药物开发的合适候选物。

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