用聚乙二醇对重组白细胞介素2进行化学修饰可增强其在小鼠Meth A肉瘤模型中的效力。
Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model.
作者信息
Katre N V, Knauf M J, Laird W J
出版信息
Proc Natl Acad Sci U S A. 1987 Mar;84(6):1487-91. doi: 10.1073/pnas.84.6.1487.
Abstract
Recombinant human interleukin 2 purified from Escherichia coli has limited solubility at neutral pH and a short circulatory half-life. This recombinant interleukin 2 was chemically modified by an active ester of polyethylene glycol. The modified interleukin 2 was purified by hydrophobic interaction chromatography and characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and isoelectric focusing. This conjugate was compared to unmodified recombinant interleukin 2 in vitro and in vivo. Covalent attachment of the hydrophilic polymer polyethylene glycol enhanced the solubility of interleukin 2, decreased its plasma clearance, and increased its antitumor potency in the Meth A murine sarcoma model.
摘要
从大肠杆菌中纯化得到的重组人白细胞介素2在中性pH下溶解度有限，循环半衰期较短。这种重组白细胞介素2通过聚乙二醇活性酯进行化学修饰。修饰后的白细胞介素2通过疏水相互作用色谱法进行纯化，并通过十二烷基硫酸钠/聚丙烯酰胺凝胶电泳和等电聚焦进行表征。将该缀合物与未修饰的重组白细胞介素2进行体内外比较。亲水性聚合物聚乙二醇的共价连接提高了白细胞介素2的溶解度，降低了其血浆清除率，并增强了其在Meth A小鼠肉瘤模型中的抗肿瘤效力。
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