Method for producing peptide

Abstract

The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an -SMe group; (b) allowing the -SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

What is claimed is: 
     
         1 . A method for producing a peptide comprising an amino acid residue having an —OH group, comprising converting an —SH group of a peptide comprising an amino acid residue having the —SH group to the —OH group, wherein said method comprises the following steps (a) to (c):
 (a) allowing the —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; 
 (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent; and 
 (c) modifying the reaction conditions to become more basic than the conditions in the step (b); 
 wherein the amino acid residue having the —SH group is a threonine derivative A residue represented by the following Formula (1), 
 
       
         
           
           
               
               
           
         
       
       the —SH group of the threonine derivative A residue in the peptide reacts with the methylating agent in the step (a), and the threonine derivative A residue is converted to a threonine residue by converting the —SH group to the —OH group. 
     
     
         2 . The method for producing a peptide according to  claim 1 , wherein the production method further comprises the following step (o) before the step (a), and the —SH group of the threonine derivative A residue represented by the following Formula (1) in the peptide obtained in the step (o) reacts with a methylating agent in the step (a):
 (o) ligating a first peptide containing, at the C-terminus thereof, an amino acid residue in which a carboxyl group is substituted with a thioester group represented by the formula —C(═O)—SR (wherein R is selected from a benzyl group, an aryl group, and an alkyl group, which may be substituted with substituents), to a second peptide containing, at the N-terminus thereof, a threonine derivative A residue according to a ligation method to obtain a peptide comprising a threonine derivative A represented by the following Formula (1) 
 
       
         
           
           
               
               
           
         
       
       as an amino acid residue. 
     
     
         3 . A method for producing a peptide comprising an amino acid residue having an —OH group, comprising converting an —SH group of a peptide comprising an amino acid residue having the —SH group to the —OH group, wherein said method comprises the following steps (a) to (c):
 (a) allowing the —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; 
 (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent; and 
 (c) modifying the reaction conditions to become more basic than the conditions in the step (b); 
 wherein the peptide comprising an amino acid residue having the —SH group is a glycopeptide having an O-linked sugar chain, and a glycopeptide comprising an amino acid residue having the —OH group is obtained. 
 
     
     
         4 . A method for producing a peptide comprising an amino acid residue having an —OH group, comprising converting an —SH group of a peptide comprising an amino acid residue having the —SH group to the —OH group, wherein said method comprises the following steps (a) to (c):
 (a) allowing the —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; 
 (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent; and 
 (c) modifying the reaction conditions to become more basic than the conditions in the step (b); 
 wherein the peptide comprising an amino acid residue having the —SH group is a glycopeptide, and a glycopeptide comprising an amino acid residue having the —OH group is obtained; and 
 wherein the amino acid residue having the —SH group is a threonine derivative A represented by the following Formula (1), and the production method further comprises the following step (o) before the step (a), and the —SH group of the threonine derivative A residue in the glycopeptide obtained in the step (o) reacts with the methylating agent in the step (a): 
 (o) ligating a first glycopeptide whose C-terminus is represented by the following formula:
   -sugar Asn-X—C(═O)—SR
 
 
 
       (wherein sugar Asn represents a sugar chain-added asparagine, 
       X represents a portion other than a carboxyl group of any given amino acid residue other than proline, and 
       R is selected from a benzyl group, an aryl group, and an alkyl group, which may be substituted with substituents), to a second peptide containing a threonine derivative A residue at the N-terminus thereof according to a ligation method to obtain a glycopeptide containing a threonine derivative A represented by the following Formula (1): 
       
         
           
           
               
               
           
         
       
       as an amino acid residue. 
     
     
         5 . A glycopeptide having a structure represented by the following formula:
   -sugar Asn-X—Y—
   wherein sugar Asn represents a sugar chain-added asparagine,   X represents any given amino acid residue other than proline, and   Y represents a threonine derivative A residue represented by Formula (2):