Peptide crosslinking agent and crosslinked peptide which is crosslinked using said crosslinking agent

A method for producing a protein(s) or a peptide(s) bound to a reactive functional group which is represented by the following formula:

• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional group;
• comprising:
• reacting a crosslinked protein(s) or peptide(s) represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, and Protein/Peptide A and Protein/Peptide B are optionally the same or different;
• and NH2-L-Z (L represents a linker and Z represents the reactive functional group), to thereby introduce the reactive functional group to a crosslinked portion of the crosslinked protein(s) or peptide(s).

A method for producing a complex of a protein(s) or a peptide(s) and a drug represented by the following formula:

• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and D represents the drug;
• comprising:
• reacting a protein(s) or a peptide(s) bound to a reactive functional group which is represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional group;
• and the drug having another functional group reactive with the reactive functional group, to thereby bind the drug to a crosslinked portion of the crosslinked protein(s) or peptide(s).

A method for producing an IgG-Fc region-containing molecule bound to an Fc-binding peptide having a reactive functional group Z,

• wherein the Fc-binding peptide is represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, L represents a linker and Z represents the reactive functional group;
• comprising
• reacting an IgG-Fc region-containing molecule bound to a crosslinked Fc-binding peptide represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group;
• and NH2-L-Z (L represents a linker and Z represents the reactive functional group), to thereby introduce the reactive functional group into a crosslinked portion in the crosslinked Fc-binding peptide.

A method for producing an IgG-Fc region-containing molecule bound to an Fc-binding peptide having a drug D,

• wherein the Fc-binding peptide is represented by the following formula:
• comprising:
• reacting an IgG-Fc region-containing molecule bound to an Fc-binding peptide(s) having a reactive functional group Z,
• wherein the Fc-binding peptide is represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, L represents a linker and Z represents the reactive functional group;
• and the drug having another functional group reactive with the reactive functional group Z, to thereby bind the drug to a crosslinked portion of a crosslinked protein or peptide.

A method for producing a crosslinked protein or peptide in which at least two thiol groups are bound as,

• wherein the crosslinked protein or peptide is represented by the following formula:
• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, and Protein/Peptide represents a protein or a peptide;
• comprising:
• synthesizing the protein or peptide by an Fmoc method;
• and
• using a compound represented by the following formula, instead of at least one cysteine residue, in the synthesis

A method for producing a protein or a peptide bound to a reactive functional group or drug-represented by the following formula:

• wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, L represents a linker, Z represents the reactive functional group and D represents a drug;
• comprising:
• synthesizing the protein or peptide by an Fmoc method;
• and
• using a compound represented by the following formula, instead of at least one cysteine residue, in the synthesis