Linaclotide solid-phase synthesis method

• Main Authors: CHANG MIN, DONG SHOULIANG, ZHU CHUNYAN, CAI YUE
• Format: Patent
• Language: English
• Published: 14.10.2015
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

The invention discloses a linaclotide solid-phase synthesis method, and belongs to the biochemical technical field. The method includes the following steps: (1) preparation of linaclotide resin; (2) cutting the linaclotide linear peptide resin obtained in the step (1), to obtain a protection group linear peptide containing Cys(Acm) and Cys(tBu); (3) oxidizing to form a first disulfide bond, to obtain a monodisulfide cyclopeptide; (4) removing an Acm protection group in the monodisulfide cyclopeptide, to obtain a dual disulfide cyclopeptide; (5) removing a tBu protection group of the dual disulfide cyclopeptide, to obtain a trisdisulfide cyclopeptide; and (6) purifying the trisdisulfide cyclopeptide by HPLC, and freeze-drying to obtain linaclotide. The process has the characteristics of simple reaction operation, easy post-processing, low cost, high yield, and considerable economic and practical values, and besides, has wide application prospect in the polypeptide drug design and synthesis field.