NOVEL PEPTIDE DIMERS AS AGONISTS OF THE ERYTHROPOIETIN (EPO) RECEPTOR, AND ASSOCIATED METHODS OF SYNTHESIS AND USE

摘要

Novel peptide dimers are provided that bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist. The novel compounds have a first peptide chain RSUP1/SUP and a second peptide chain RSUP2/SUP, wherein RSUP1/SUP and RSUP2/SUP may be the same or different, and are linked through a linking moiety. RSUP1/SUP is approximately 10 to 40 amino acid residues in length and comprises the sequence XSUB3/SUBXSUB4/SUBXSUB5/SUBGPXSUB6/SUBTXSUB7/SUBXSUB8/SUBXSUB9/SUB (SEQ ID NO: 1) wherein XSUB3/SUB is C or Hoc, XSUB4/SUB is R, H, L or W, XSUB5/SUB is M, F, I or nor-leucine (J), XSUB6/SUB is any one of the 20 genetically coded L-amino acids or J, XSUB7/SUB is W, 1-naphthylalanine (B) or 2-naphthylalanine (U), XSUB8/SUB is D, E, I, L or V, and XSUB9/SUB is C or Hoc. Similarly, RSUP2/SUP comprises the sequence X'SUB3/SUBX'SUB4/SUBX'SUB5/SUBGPX'SUB6/SUBTX'SUB7/SUBX'SUB8/SUBX'SUB9/SUB (SEQ ID NO: 2) wherein X'SUB3/SUB is C or Hoc, X'SUB4/SUB is R, H, L or W, X'SUB5/SUB is M, F, I or J, x'SUB6/SUB is any one of the 20 genetically coded L-amino acids or J, X'SUB7/SUB is W, B or U, X'SUB8/SUB is D, E, I, L or V and X'SUB9/SUB is C or Hoc. Methods for synthesizing the compounds are provided as well, as are pharmaceutical compositions and methods of use.