SMALL PEPTIDES AS POTENT MIMETICS OF THE PROTEIN HORMONE ERYTHROPOIETIN

Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the rece ptor for the cytokine erythropoietin (EPO). In a panel of in vitro bio logical assays, the peptides act as full agonists and they can also st imulate erythropoiesis in mice. These agonists are represented by a 14 -amino acid disulfide-bonded, cyclic peptide with the minimum consensu s sequence YXCXXGPXTWXCXP, where X represents positions allowing occup ation by several amino acids. The amino acid sequences of these peptid es are not found in the primary sequence of EPO. The signaling pathway s activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the desig n of small molecule mimetics of EPO.