Method for synthesizing etelcalcetide
AssigneeHybio Pharmaceutical Co., Ltd.
InventorsYonghan Chen, Pengcheng Mi, Anjin Tao, Jiancheng Yuan
Life of this patent
Estimating the term…
Abstract
Provided is a method for solid phase synthesis of Etelcalcetide, comprising synthesizing Etelcalcetide backbone peptide resin, removing the side chain protecting group of Cys in the peptide chain, and then activating the sulfydryl group of the Cys side chain on the peptide resin with 2,2′-dithiodipyridine and constructing a disulfide bond with L-Cys, such that a crude Etelcalcetide peptide is obtained by cleaving. The method does not require undergoing multi-step purification, the yield and purity of the obtained crude peptide are relatively high, and the total yield of the refined peptide after purification is greatly increased.
Claims10
A method for synthesizing Etelcalcetide, comprising the steps of:
- step 1:
- synthesizing by solid-phase synthesis a peptide resin of fragment A, in which protecting groups are coupled to side chains of D-Cys and D-Arg in the amino acid sequence shown in SEQ ID NO:
- 1, an amino resin is coupled to C-terminus of the amino acid sequence shown in SEQ ID NO:
- 1 and N-terminus is acetylated;
- step 2:
- removing the protecting group from the side chain of D-Cys in the peptide resin of fragment A to obtain a peptide resin of fragment B;
- step 3:
- activating sulfhydryl group of the side chain of D-Cys in the peptide resin of fragment B with 2,2′-dithiodipyridine to obtain a peptide resin of fragment C;
- and
- step 4:
- coupling L-Cys coupled with a protecting group at the N-terminus thereof to the peptide resin of fragment C in a coupling system to construct a disulfide bond, obtaining a fully protected peptide resin, and adding a cleaving solution to remove all protecting groups and amino resin to obtain a crude peptide of Etelcalcetide.
Dependencies are inferred from the claim text.