Wrighton N C, Farrell F X, Chang R, Kashyap A K, Barbone F P, Mulcahy L S, Johnson D L, Barrett R W, Jolliffe L K, Dower W J
Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304, USA.
Science. 1996 Jul 26;273(5274):458-64. doi: 10.1126/science.273.5274.458.
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.
利用随机噬菌体展示肽库和亲和选择方法，分离出与细胞因子促红细胞生成素（EPO）受体结合并激活该受体的小肽。在一系列体外生物学试验中，这些肽充当完全激动剂，它们还能刺激小鼠的红细胞生成。这些激动剂由一个14个氨基酸的二硫键连接的环肽代表，其最小共有序列为YXCXXGPXTWXCXP，其中X代表可被几种氨基酸占据的位置。这些肽的氨基酸序列在EPO的一级序列中未发现。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。
