Peptides and processes for producing cyclic peptides

A process for producing a cyclic peptide or an acid addition salt or complex compound thereof which comprises subjecting a peptide of the following general formula (IVa) ##STR99## wherein F means a hydroxyl group, an active ester residue, Ser-OH, Ser-Asn-OH, Ser-Asn-Leu-OH, Ser-Asn-Leu-Ser-OH (SEQ ID NO:

• 43) or Ser-Asn-Leu-Ser-Thr-OH (SEQ ID NO:
• 44);
• G means H-Ser-Asn-Leu-Ser-Thr (SEQ ID NO:
• 43), H-Asn-Leu-Ser-Thr (SEQ ID NO:
• 34), H-Leu-Ser-Thr, H-Ser-Thr or H-Thr or a hydrogen atom, provided that F and G form by condensation reaction Ser-Asn-Leu-Ser-Thr (SEQ ID NO:
• 44);
• and each amino acid residue may have been protected with a protective group;
• W means a hydroxyl group or a peptide residue of the general formula (VII)
• -A1-Leu-A2-OH (VII)
• where A1 means Val or Met;
• A2 means Ser or Gly;
• and each amino acid residue may have been protected with a protective group,
• to a cyclization reaction in the presence of an alkali metal halide, and
• condensing, by the technique of solid phase synthesis, the resultant peptide of the following general formula (V) (SEQ ID NO:
• 4):
• ##STR100## wherein W is as defined above;
• and each amino acid residue may have been protected with a protective group,
• with a peptide-resin synthesized on a solid phase reaction resin and having the following general formula (VI) ##STR101## wherein:
• Xaa at position 1 is Lys, Thr or Ala;
• Xaa at position 2 is Leu or Tyr;
• Xaa at position 3 is Ser, Thr or Trp;
• Xaa at position 4 is Gln, Lys or Arg;
• Xaa at position 5 is Glu, Asp or Asn;
• Xaa at position 6 is Leu or Phe;
• Xaa at position 7 is His or Asn;
• Xaa at position 8 is Lys or Asn;
• Xaa at position 9 is Leu, Phe or Thr;
• Xaa at position 10 is Gln or His;
• Xaa at position 11 is Thr or Arg;
• Xaa at position 12 is Tyr or Phe;
• Xaa at position 13 is Pro or Ser;
• Xaa at position 14 is Arg, Gly or Gln;
• Xaa at position 15 is Thr or Met;
• Xaa at position 16 is Asp, Ala, Asn or Gly;
• Xaa at position 17 is Val, Ile, Thr or Phe;
• Xaa at position 19 is Ala, Val, Pro or Ser;
• Xaa at position 20 is Gly or Glu;
• Xaa at position 21 is Thr or Ala;
• and Pro at position 22 is attached to a resin support;
• or having the following general formula (VIII) ##STR102## wherein:
• Xaa at position 1 is Val or Met;
• Xaa at position 3 is Ser or Gly;
• Xaa at position 4 is Lys, Thr or Ala;
• Xaa at position 5 is Leu or Tyr;
• Xaa at position 6 is Ser, Thr or Trp;
• Xaa at position 7 is Gln, Lys or Arg;
• Xaa at position 8 is Glu, Asp or Asn;
• Xaa at position 9 is Leu or Phe;
• Xaa at position 10 is His or Asn;
• Xaa at position 11 is Lys or Asn;
• Xaa at position 12 is Leu, Phe or Thr;
• Xaa at position 13 is Gln or His;
• Xaa at position 14 is Thr or Arg;
• Xaa at position 15 is Tyr or Phe;
• Xaa at position 16 is Pro or Ser;
• Xaa at position 17 is Arg, Gly or Gln;
• Xaa at position 18 is Thr or Met;
• Xaa at position 19 is Asp, Ala, Asn or Gly;
• Xaa at position 20 is Val, Ile, Thr or Phe;
• Xaa at position 22 is Ala, Val, Pro or Ser;
• Xaa at position 23 is Gly or Glu;
• Xaa at position 24 is Thr or Ala;
• and Pro at position 25 is attached to a resin support;
• each amino acid residue may have been protected with a protective group;
• provided, however, that when W is a hydroxyl group, SEQ ID NO:
• 42 is used and when W is -A1-Leu-A2-OH, SEQ ID NO:
• 41 is used.