Small peptides as potent mimetics of the protein hormone erythropoietin
Small peptides as potent mimetics of the protein hormone erythropoietin
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DOI：
10.1126/science.273.5274.458
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发表时间：
1996-07-26
期刊：
影响因子：
56.9
通讯作者：
Dower, WJ
中科院分区：
文献类型：
--
作者：
Wrighton, NC;Farrell, FX;Dower, WJ
随机噬菌体展示肽库和亲和选择性方法用于分离结合并激活细胞因子促红细胞生成素（EPO）受体的小肽。在一组体外生物测定中，肽作为完全激动剂，它们也可以刺激小鼠的红细胞生成。这些激动剂由具有最小共有序列YXCXXGPXTWXCXP的14-氨基酸二硫键结合的环状肽表示，其中X表示允许被几个氨基酸占据的位置。这些肽的氨基酸序列在EPO的一级序列中没有发现。这些肽激活的信号通路似乎与天然配体诱导的信号通路相同。这一发现可能为EPO小分子模拟物的设计奠定基础。
Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14-amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.