Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof
The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WX 1 X 2 X 3 W, where W is tryptophan, and X 1 , X 2 and X 3 are amino acids, with the proviso that when one of X 1 , X 2 or X 3 is W, the remaining two of X 1 , X 2 or X 3 cannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease.
1. An isolated polypeptide, wherein said isolated polypeptide inhibits the binding of IL-23 to IL-23 receptor and the IL-23-mediated signaling, and wherein said isolated polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO: 166.
2. An isolated polypeptide of 9-18 amino acids in length, wherein said isolated polypeptide comprises a core structure that consists of the amino acid sequence of WVDYW (SEQ ID NO: 150) or WQDYW (SEQ ID NO: 151), wherein said isolated polypeptide inhibits the binding of IL-23 to IL-23 receptor and the IL-23-mediated signaling.
3. The isolated polypeptide of claim 2 , wherein said isolated polypeptide is selected from the group consisting of SEQ NO: 152, SEQ ID NO: 153, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 163, and SEQ ID NO: 164.
4. The isolated polypeptide of claim 2 , wherein said isolated polypeptide is a cyclic peptide through a disulfide bridge between two cysteine residues.
5. The isolated polypeptide of claim 2 , wherein said isolated polypeptide is 12 amino acids in length.