Method for preparing salmon calcitonin acetate by fragment condensation

A technology for salmon calcitonin acetate and salmon calcitonin, which is applied in the fields of peptide preparation, calcitonin, chemical instruments and methods, etc., can solve the problems of difficult salmon calcitonin, low yield, and difficulty in product purification.

Active Publication Date: 2014-12-03
HAINAN JIANKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a method for preparing salmon calcitonin acetate using solid-liquid phase combination fragment condensation for the shortcomings of low yield, difficult product purification, and difficulty in obtaining high-purity salmon calcitonin in the existing synthesis method element, improved yield and purity, low cost, conducive to large-scale production

Method used

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  • Method for preparing salmon calcitonin acetate by fragment condensation
  • Method for preparing salmon calcitonin acetate by fragment condensation
  • Method for preparing salmon calcitonin acetate by fragment condensation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Example 1: Preparation of Acetate Salmon Calcitonin in Three Fragments.

[0086] 1. Synthesis of resin

[0087] 1.1 Synthesis of Fmoc-Gly-2-chloro-trityl chloride resin: add 2-chloro-trityl chloride resin (5g, substitution value 0.75mmol / g resin, 1eq.) into 150mL peptide synthesizer, use 60mL DCM washes the swollen resin. The solvent was drained, and a 30 mL DCM solution of Fmoc-Gly-OH (1.5 eq.) and DIEA (3 eq.) was added. The mixture was stirred for 1 hour under an argon atmosphere. Add 10mL of chromatographic methanol (2ml / g resin) to block the active part on the resin for 30 minutes. The resin bed was drained, washed with 3×60 mL DMF, 3×60 mL DCM, 3×60 mL MeOH, and dried to constant weight under vacuum to obtain 5.8107 g of Fmoc-Gly-2-chloro-trityl chloride resin. The amount of Fmoc in the piperidine deprotection solution was measured by ultraviolet spectrophotometry, and the resin loading was 0.53mmol / g.

[0088] 1.2 Synthesis of Fmoc-Pro-2-chloro-trityl chloride resi...

Embodiment 2

[0155] Example 2: Preparation of Acetate Salmon Calcitonin with Four Fragments.

[0156] 1. Resin synthesis

[0157] 1.1 Synthesis of Fmoc-Thr(tBu)-2-chloro-trityl chloride resin: add 2-chloro-trityl chloride resin (5g, substitution value 0.75mmol / g resin, 1eq.) into 150mL peptide synthesizer , Swell the resin with 60 mL DCM. The solvent was drained, and a 30 mL DCM solution of Fmoc-Thr(tBu)-OH (1.5eq.) and DIEA (3eq.) was added. The mixture was stirred for 1 hour under an argon atmosphere. Add 10mL of chromatographic methanol (2ml / g resin) to block the active part on the resin for 30 minutes. The solvent was drained, washed with 3×60 mL DMF, 3×60 mL DCM, 3×60 mL MeOH, and vacuum filtered and dried to constant weight to obtain 6.112 g of Fmoc-Thr(tBu)-2-chloro-trityl resin. The amount of Fmoc in the piperidine deprotection solution was measured by ultraviolet spectrophotometry, and the resin loading was 0.50 mmol / g.

[0158] 1.2 The synthesis of Fmoc-Pro-2-chloro-trityl resin is...

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Abstract

The invention discloses a method for preparing salmon calcitonin acetate by fragment condensation, which comprises the following steps: 1) synthesizing fragment sequences of salmon calcitonin (1st-10th, 11th-23rd, 24th-32nd or 24th-31st amino acids) on a solid-phase vector by solid-phase synthesis; 2) sequentially coupling the fragment in the liquid phase to form full-protection salmon calcitonin; and 3) cracking the full-protection salmon calcitonin to obtain salmon calcitonin crude peptides, and carrying out high-efficiency liquid-phase purification salt exchange to obtain the salmon calcitonin acetate pure peptides. The method for preparing salmon calcitonin acetate by combining solid/liquid phase and fragment condensation enhances the yield and purity, and is low in cost and beneficial to large-scale production.

Description

Technical field [0001] The invention relates to the field of pharmacy, in particular to a method for preparing acetic acid salmon calcitonin by fragment condensation. Background technique [0002] Salmon calcitonin is a single chain composed of 32 amino acids, and its N-terminal 7 amino acids are cyclized into disulfide bonds. Because salmon calcitonin has a high affinity for the binding site of human calcitonin receptor, it has better effect and longer action time than synthetic mammalian calcitonin. Salmon calcitonin inhibits osteoclast activity through its specific receptor. In the case of increased bone resorption, such as osteoporosis, it can significantly reduce bone turnover, and even normalize bone turnover. It has been proved that salmon calcitonin has analgesic effects on animal models and humans, which may be the result of direct action on the central nervous system. Therefore, it is mainly used clinically to treat early and late postmenopausal osteoporosis and seni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/585C07K1/10C07K1/06C07K1/04
CPCC07K14/585
Inventor 常民王锐彭雅丽薛宏祥
Owner HAINAN JIANKE PHARMA
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