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Method for preparing ziconotide

2013 
The invention belongs to the technical field of polypeptide drugs, and particularly relates to a method for preparing ziconotide, and the method is used for solving the technical problems of difficult separation and purification and low total product yield and purity in the existing preparation methods. The method comprises the following steps of: preparation of ziconotide linear peptide resin based on a solid phase polytide method, acidolysis for obtaining a ziconotide linear peptide crude product, oxidation for obtaining a ziconotide crude product and purification for obtaining a ziconotide purified product, wherein the solid phase polytide method comprises the following steps of: preparing ziconotide linear peptide resin by sequentially connecting corresponding protected amino acid or protected amino acid fragment in the following sequence starting from amino resin through a solid phase coupling synthesis method: R-Cys(Trt)-X(Boc)-X(Boc)-Ala-Lys(Boc)-Cys(Trt)-Ser(tBu)-Arg(Pbf)-Leu-Met-Tyr(tBu)-Asp(OtBu)-Cys(Trt)-Cys(Trt)-Y(tBu)-Ser(tBu)-Cys(Trt)-Arg(Pbf)-Z(tBu)-Lys(Boc)-Cys(Trt)-amino resin, wherein R is Fmoc, Boc or H, X is Lys-Gly, Y is Thr-Gly, and Z is Ser-Gly. The invention provides a novel method for shortening the production period and improving the product purity and the product yield.
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