Patent GB-1119353-A (GB)
Title: Peptides having an adrenocorticotropic hormone action and process for their manufacture
IPC: C07K5/083
Filed: 1965-08-06
Abstract: A peptide that differs from an ACTH-active peptide containing 16-39 amino acid residues and having an N-terminal amino acid residue with L-configuration, solely in that the N-terminal amino acid residue has D-configuration, acid addition salts, complexes and amino and carboxylic acid blocked derivatives thereof are prepared by standard methods of peptide synthesis.  Preferred peptides are those that differ from an (all-L)-ACTH-active peptide containing a 16-39 amino acid residue sequence (commencing at the N-terminus) of a natural corticotrophin, in which at least one of the amino acid residues in the positions 1 to 5, 17, 18 and 25 to 33 may be replaced by the residue of another natural a -amino acid or of a homologue thereof, solely in that the N-terminal amino acid residue has D-configuration. The following compounds are prepared as starting materials or as intermediates: BOC-D-Serine, BOC - D - Ser - Tyr - Ser - Met - OMe and -NHNH2; BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - GlyOH; BOC - D - Ser - Tyr+ - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; BOC - D - alanine; BOC - D - Ala - Tyr - Ser - Met - NHNH2; BOC - D - Ala - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - GlyOH; BOC - D - Ala - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; Z - Arg - Pro - OtBu; Z - Arg - Arg - Pro - OtBu; H-Arg - Arg - Pro -OtBu; Z - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - OtBu; H - Lys(BOC) - Pro - Val - Gly - Lys - Lys(BOC) - Arg - Arg - Pro OtBu; BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - OtBu; Z - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; H - Pro - Val - Lys - Val - Tyr - Pro OtBu; Z - Orn(BOC) - OH; its p-nitrophenyl ester and its hydrophthalimide ester; Z - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; H - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; Z - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBOC; H - Orn(BOC) - Orn(BOC) - Pro - Val - Lys (BOC) - Val - Tyr - Pro - OtBu; Z - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys (BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Orn - Tyr - Pro OtBu; H - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro OtBu - tosylate; BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys - (BOC) - Lys(BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu; H - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - NH2; BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - NH2; BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - ProVal - Lys(BOC) - Val - Tyr - Pro - Asp(OtBu) - Gly - Ala - Glu(OtBu) - Asp(OtBu) - Glu(NH2) - Leu - Ala - Glu(OtBu) - Ala - Phe - Pro - Leu - Glu(OtBu) - Phe - OtBu; BOC - Tyr - Gly - Ome; H - Tyr - Gly - Ome, HCl; BOC - D - Ser - Tyr - Gly - Ome; BOC - D - Ser - Tyr - Gly - OH; BOC - D - Ser - Tyr - Gly - Met - Ome and -NHNH2; Z - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu - triacetate; H - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu - tetra-acetate and BOC - D - Ser - Tyr - Gly - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu.  Pharmaceutical compositions comprise the peptides of the invention in admixture or in conjunction with a suitable carrier.  The compositions may be formulated for enteral or parenteral administration.