PEPTIDE CONJUGATES MODIFIED N- AND/OR C-TERMINALLY BY SHORT CHARGED PEPTIDE CHAINS

摘要

Disclosed are a variety of peptide conjugates represented by the following general formula (I): R1-Z-X-Z'-R2, wherein X represents a hexapeptide of the formula (II): A?1-A2-A3-A4-A5-A6¿ wherein A1 represents Arg, Lys, or His, A2 represents Tyr, Trp, or Phe, A3 represents Tyr, Asn, Trp or Phe, A4 represents Lys, Arg or His, A5 represents Phe, Tyr, Trp, Leu, Val or Ile, and A6 represents Arg, Lys, or His and wherein each amino acid residue in said hexapeptide may be in the L or D form; Z represents a charged peptide chain of from 4 to 20 amino acid residues having the D or L configuration or is missing; and Z' represents a charged peptide chain of from 4 to 20 amino acid residues having the D or L configuration or is missing, providing that not both of Z and Z' are missing; R¿1? represents H or an acyl group; R2 represents NR3R4 where each of R3 and R4 independently represents hydrogen, C(1-6)alkoxy, aryloxy, or a lower alkyl as defined herein; or R2 represents OH; the peptide conjugates of formula (I) being optionally further linked to a transport moiety; and salts, hydrates and solvates thereof, and C-terminally amidated or esterified derivatives thereof with suitable organic or inorganic acids, including methods or making and using such conjugates. Also provided are antibodies that specifically bind the peptide conjugates. The present invention has a wide spectrum of important applications including use in the treatment of disorders impacted by nociceptin and related opioid-like peptides.