Patent ID: 6682740
Filing Date: 2004-01-27
Classification: A61K,C07K

Abstract:
A molecule consisting of:(a) a peptide consisting of the sequence of amino acids 50-76 (residues 50-76 of SEQ ID NO:1) of the human complement C3a; (b) a fragment of (a) having at least five amino acid residues in which one or more of the following deletions from (a) have been made: the residues at positions 50, 50-53, 50-54, 50-55, 50-56, 57-76, 61-76, 62-76, 63-76, 64-76, 65-76, 66-76, or 70-76, which fragment has the property of inhibiting the IgE-mediated triggering and/or the Fc&egr;RI-induced secretory response of mucosal mast cells; (c) an analog of (a) or (b) in which one or more of the following additions and/or substitutions are made: the Asp-Cys residues at 55-56 are substituted by Arg-Arg when at the N-terminus, the Cys residue at position 56 is substituted by Arg when at the N- or C-terminus, when a Cys residue at position 56 or 57 is at the N-terminus, it is acylated by a non-polar lower carboxylic acyl group, the Cys-Cys residues 56-57 are substituted by Ala-Ala or Ser-Ser, the Tyr residue at position 59 is substituted by another aromatic amino acid, the Ile residue at position 60 is substituted by Gly, the Thr residue at position 61 is substituted by Arg or, when at the C-terminus of the molecule, by Agm, the Glu residue at position 62 is substituted by Lys or Arg, the Leu residue at position 63 is substituted by Arg or, when at the C-terminus of the molecule, by Agm, the Arg residue at position 64 is substituted by any positively charged amino acid residue, the Arg residue at position 65 is substituted by Glu, the Ala residue at position 68 is substituted by Arg, the Arg residue at position 69 is substituted by Lys, the Ala residue at position 70 is substituted by Asp, the Ser residue at position 71 is substituted by His, the His residue at position 72 is substituted by Val, the Leu residue at position 73 is substituted by Ile, Ala or Gly, and an agmatine (Agm) residue is added at the C terminal side of the Ala at position 76, which analog has the property of inhibiting the IgE-mediated triggering and/or the Fc&egr;RI-induced secretory response of mucosal mast cells;(d) a chemical derivative of (a), (b) or (c) formed by modification of a free carboxy, amino or hydroxy group of one or more amino acid residues so as to add one or more chemical moieties not normally a part of the peptide molecule, without changing one amino acid residue to a different amino acid residue, which derivative has the property of inhibiting the IgE-mediated triggering and/or the Fc&egr;RI-induced secretory response of mucosal mast cells; or (e) a salt of (a), (b), (c) or (d).