Selective peptide antagonists
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
1. A compound, comprising:
a composite polypeptide sequence comprising sequence fragments from binding site of γc-family cytokines, the γc-family cytokines being selected from the group consisting of IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21; and
a polyethylene glycol (PEG) unit;
wherein the compound is represented by H-Cys(acetylamino-propyl-mPEG40k) -Gly-Ser-Gly-Gly-Ile-Lys-Glu-Phe-Leu-Gln-Arg-Phe-Ile-His-Ile-Val-GIn-Ser-Ile- Il e-Asn -Thr-Ser-NH 2 (SEQ ID NO: 133).