公开(公告)号：US5206344A

公开(公告)日：1993-04-27

申请号：US142467

申请日：1988-01-11

申请人： Nandini Katre ,  Robert F. Halenbeck ,  Robert J. Goodson ,  Peter C. McCabe ,  Michael J. Knauf

发明人： Nandini Katre ,  Robert F. Halenbeck ,  Robert J. Goodson ,  Peter C. McCabe ,  Michael J. Knauf

IPC分类号： A61K38/20 ,  A61K38/21 ,  A61K47/48 ,  C07K1/107

CPC分类号： A61K47/48215 ,  A61K38/2013 ,  A61K38/215 ,  A61K47/48476 ,  C07K1/1077 ,  Y10S930/141

摘要： Muteins of IL-2 in which one of the amino acids of the mature native sequence of IL-2 is replaced by a cysteine residue are prepared and conjugated through the replaced cysteine residue to a polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols, wherein said homopolymers are unsubstituted or substituted at one end with an alkyl group. These muteins are made via host expression of mutant genes encoding the muteins that have been changed from the genes for the parent proteins by site-directed mutagenesis. In addition, other species of IL-2 may be conjugated via the cysteine residue at position 125 of the mature IL-2 protein that is not necessary for the biological activity of the IL-2.

摘要翻译： 制备其中IL-2的成熟天然序列的一个氨基酸被半胱氨酸残基取代的IL-2的突变蛋白，并通过所述替换的半胱氨酸残基与选自聚乙二醇均聚物或聚氧乙烯化多元醇的聚合物缀合，其中所述 均聚物是未取代的或在一端被烷基取代。 这些突变蛋白是通过宿主表达编码突变蛋白的突变基因，通过定点突变从母体蛋白的基因中改变的突变蛋白。 此外，IL-2的其它物质可以通过成熟IL-2蛋白的125位的半胱氨酸残基而被结合，这对于IL-2的生物活性是不必要的。