Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.
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