US 12,479,882 B2
Preparation method of setmelanotide by cyclization of disulfide bond in solid phase
Yao-Lung Hsu, New Taipei (TW); Chun-I Lee, New Taipei (TW); Chun-Ling Lin, New Taipei (TW); Ya-Ling Huang, New Taipei (TW); and Jia-Chun Lee, New Taipei (TW)
Assigned to CHUNGHWA CHEMICAL SYNTHESIS & BIOTECH CO. LTD., New Taipei (TW)
Filed by Chunghwa Chemical Synthesis & Biotech Co. Ltd., New Taipei (TW)
Filed on May 4, 2023, as Appl. No. 18/312,203.
Claims priority of application No. 111148202 (TW), filed on Dec. 15, 2022.
Prior Publication US 2024/0199685 A1, Jun. 20, 2024
Int. Cl. C07K 7/00 (2006.01); C07K 1/06 (2006.01); C07K 1/107 (2006.01); C07K 7/54 (2006.01)
CPC C07K 1/061 (2013.01) [C07K 1/107 (2013.01); C07K 7/54 (2013.01)] 13 Claims
 
1. A preparation method of setmelanotide by cyclization of a disulfide bond in a solid phase, comprising:
(a) preparation of a peptide resin without cyclization of a setmelanotide protective group:
using an amino resin as an initial resin, and then sequentially connecting amino acids with a protective group in a reverse direction according to an amino acid sequence of setmelanotide to obtain the peptide resin without cyclization of a setmelanotide protective group;
(b) cyclization of a disulfide bond of the peptide resin without cyclization of a setmelanotide protective group: putting the peptide resin without cyclization of a setmelanotide protective group in a reaction solvent containing an oxidizing agent, adding a reducing agent to remove the unreacted oxidizing agent, and finally adding a cleavage reagent to obtain a cyclized setmelanotide solution; and
(c-1) dropping the cyclized setmelanotide solution into an ether for precipitation to obtain crude setmelanotide, or
(c-2) adding the cyclized setmelanotide solution into a dilution solution to obtain a crude setmelanotide solution.