Process for Producing Self-Assembling Peptide Derivatives

A process for producing a peptide derivative represented by general formula (VII):

• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Ala-Leu-Arg-Leu-Asp-
• Leu-Arg-NHT2•n(acid)
• (wherein n represents a number satisfying the equation:
• (the valence of the acid)×n=4,
• which number varies with the valence of the acid) or general formula (VIII):
• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Leu-Leu-Arg-Leu-Asp-
• Leu-Arg-NH2•n(acid)
• (wherein n represents a number satisfying the equation:
• (the valence of the acid)×n=4,
• which number varies with the valence of the acid),
• the process comprising the steps of
• serially coupling, as building blocks, Peptide derivative I represented by general formula (I):
• Arg(protecting group A)-Leu-Asp(protecting group
• B)-Leu-Arg(protecting group C)
• (wherein protecting group A and protecting group C may be the same or different, and each is an Arg side-chain protecting group that is stable under basic conditions and can be removed under highly acidic conditions;
• protecting group B is an Asp side-chain protecting group that is stable under basic conditions and can be removed under highly acidic conditions;
• and
• the amino group of the N-terminal Arg and/or the carboxy group of the C-terminal Arg may be modified) and
• Peptide derivative II represented by general formula (II):
• Leu-X-Leu
• (wherein the amino group of the N-terminal Leu and/or the carboxy group of the C-terminal Leu may be modified;
• and
• X is Ala or Leu),
• removing the side-chain protecting groups with a strong acid, and
• optionally subjecting the coupling product to a terminal deprotection step, a modification step and/or a salt exchange step.

A process for producing a tetrahydrochloric acid salt of a peptide derivative represented by general formula (XI):

• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Ala-Leu-Arg-Leu-Asp-
• Leu-Arg-NH2•4HC1
• or general formula (XII):
• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Leu-Leu-Arg-Leu-Asp-
• Leu-Arg-NH2•4HC1,
• the process comprising the step of performing a salt exchange reaction of a peptide derivative represented by general formula (VII):
• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Ala-Leu-Arg-Leu-Asp-
• Leu-Arg-NH2•n(acid)
• (wherein n represents a number satisfying the equation:
• (the valence of the acid)×n=4,
• which number varies with the valence of the acid, with the exception of the case where the acid is hydrochloric acid) and/or
• general formula (VIII):
• Ac-Arg-Leu-Asp-Leu-Arg-Leu-Leu-Leu-Arg-Leu-Asp-
• Leu-Arg-NH2•n(acid)
• (wherein n represents a number satisfying the equation:
• (the valence of the acid)×n=4,
• which number varies with the valence of the acid, with the exception of the case where the acid is hydrochloric acid)
• by treating the peptide derivative with hydrochloric acid in the presence of an organic solvent.