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Method for preparing exenatide

2013 
The invention belongs to the technical field of a method for preparing a polypeptide drug, and particularly relates to a method for preparing exenatide, which solves the technical problems of difficulty in separation and purification, low total yield and purity of the product in the traditional preparation method. The technical scheme for solving the technical problem is to provide the method for preparing the exenatide. The method comprises the steps of: preparing exenatide resin by a solid-phase peptide method, carrying out acidolysis to obtain an exenatide crude product, and finally purifying to obtain an exenatide pure product, wherein the solid-phase peptide method comprises the steps of sequentially accessing amino resin into corresponding protected amino acids or protected amino acid segments in the following sequences by a solid-phase coupling synthesis method to prepare the exenatide resin: R-W(Trt)-X(OtBu)-Thr(tBu)-Phe-Thr-(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Y(Trt)--Ser(tBu)-Z(tBu)-Ala-Pro-Pro-Pro-Ser(tBu)-amino resin, wherein R is Fmoc, Boc or H; W is His-Gly; X is Glu-Gly; Y is Asn-Gly-Gly-Pro; and Z is Ser-Gly. A novel method is provided for shortening the production period, improving the purity and yield of the product.
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