A method for preparing a linaclotide dimer

Abstract

This invention discloses a method for preparing linaclotide dimers, belonging to the field of polypeptide synthesis technology; the preparation method includes: under the action of dimethyl sulfoxide, reacting linaclotide with retained Cys... 2 Site protection base and Cys 10 The linear linaclotide peptide with site-protecting groups is oxidized to form two pairs of intramolecular disulfide bonds; using ammonium acetate aqueous solution as solvent, the Cys group of the intramolecular disulfide bond monomer is removed under the action of an oxidant. 2 Site protection base or Cys 10 The site-protecting group undergoes intermolecular oxidation to construct a monomer with five disulfide bonds; subsequent treatment with an oxidative deprotecting agent removes the remaining protecting group and completes intermolecular oxidation, yielding a linaclotide dimer. This invention overcomes the technical challenge of directional construction of multiple disulfide bonds by optimizing the construction sequence and reaction conditions of intermolecular disulfide bonds, achieving precise disulfide bond pairing, successfully synthesizing the target product, and achieving a good balance between reactant conversion and reaction selectivity.

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