The present application belongs to the technical field of
protein drugs, and relates to a preparation method of an
exenatide variant and a
polyethylene glycol conjugate thereof. Specifically, Cys 39 The preparation method of Exendin-4 adopts three-step reversed-phase
column chromatography for purification, while the preparation method of mPEG-ppMAL-Cys 39 The preparation method of Exendin-4 adopts three-step reversed-phase
column chromatography for purification, while the preparation method of mPEG-ppMAL-Cys 39 The preparation method of Exendin-4 adopts three-step reversed-phase
column chromatography for purification, while the preparation method of mPEG-ppMAL-Cys When the polypeptide is purified, three-step reversed-phase column
chromatography is used, and the acidic substance used in the second step is optimized, so that the purity and yield of the product are obviously improved. When the conjugate is purified,
ion exchange
chromatography and three-step reversed-phase column
chromatography are used in sequence, so that the purity of the product can reach more than 99.5%, and the yield is high. The
combined use of the two preparation methods can meet the needs of industrial production.