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Technology for solid phase synthesis of peptide by WANG strategy

A strategy and technology of synthesis method, applied in the production process field of bulk preparation of raw materials, can solve the problems of poor purity of crude products, increase the difficulty of purification, etc., and achieve the effects of reducing production cost, improving production feasibility, and improving purity

Inactive Publication Date: 2009-06-24
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is the inevitable result of the above two classic methods of peptide synthesis. The purity of the obtained crude product is poor, which increases the difficulty of further purification.

Method used

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  • Technology for solid phase synthesis of peptide by WANG strategy
  • Technology for solid phase synthesis of peptide by WANG strategy
  • Technology for solid phase synthesis of peptide by WANG strategy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0037] 1. Synthesis of TP5 Acylethylamide H-Arg-Lys-Asp-Val-Tyr-NHeT (1)

[0038] ①Boc-Tyr-OCH 2 - Preparation of polystyrene resin

[0039] Weigh 10g (10mmol) of chloromethyl (also known as Merrifield) resin (substitution equivalent 1mmol / g, particle size 100-200 mesh, cross-linking degree 1%), and three times the number of moles of Boc-Tyr-OH.K 2 CO 3 and 1 / 10 mole of KI were blended in 150mL DMF. The suspension was rotated and reacted on a hot bath at 60° C. for 25 h, and the reaction suspension was transferred to a No. G2 sand plate filter tube. Use DMF at about 60°C for diafiltration 5 times, about 50 mL each time. This was followed by diafiltration with the following solvents (× times): 95% EtOH × 3, DMF × 3, 50% EtOH / H 2 O×3, DMF×3, absolute ethanol×3. After fully drying, take out the resin and place it under an infrared lamp at about 50°C, and air-dry it to constant weight. It weighs 12.33g, and the weight gain is 2.33g (theoretical weight gain should be 2.445g)...

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Abstract

The invention relates to solid phase synthetic peptide technology by a WANG strategy, in particular to the synthetic mode taking six active oligopeptide as the target structure and adopting cross-matching of Boc-amino acid / strong acid-cleavage resin and Fmoc-amino acid / weak acid-cleavage resin, WANG (without acid-cleavage and nice gain) strategy for short, is adopted; finally the product with satisfactory yield and more lower cost is obtained.

Description

technical field [0001] This project involves some solid-phase synthesis methods of active peptides, which are especially suitable for economical and practical mass production of raw materials. Background technique [0002] For half a century, the solid-phase peptide synthesis method invented by Professor Merrifield has greatly promoted the development of medical science. So far, Boc / Bzl / strong acid hydrolysis resin method and Fmoc / tBut / weak acid hydrolysis resin method are the two most widely used protection strategies among many solid-phase peptide synthesis techniques. Their respective matching methods are as follows Figure 1 Show. [0003] Among the classic matching strategies mentioned above, Boc Chemical uses an acid gradient selective deprotection method. After each step of condensation, use a weak acid (such as TFA) to remove only the temporary protecting Boc group on the α-amino group; after all condensation is completed, use a strong acid (such as HF or TFMSA) to...

Claims

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Application Information

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IPC IPC(8): C07K1/04C40B50/14
CPCY02P20/55
Inventor 王德心林浩杨潇骁韩香龚喜冯鹤鹤
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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