Method for synthesizing pramlintide

A pramlintide and linear peptide technology, applied in the chemical industry, can solve the problems of reducing product yield, purification and separation column damage, production troubles, etc., and achieve the effects of low cost, high synthesis efficiency and high yield

Active Publication Date: 2020-08-07
HANGZHOU GOTOP BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in actual production, the oxidation process of pramlintide has brought great trouble to the production. After the oxidation of pramlintide is completed, it is easy to form an emulsion-like state under weakly alkaline conditions, and this state It will have a great impact on the purification and separation in the later stage. If the sample is loaded directly without filtration, it will not only damage the purification separation column, but also reduce the product yield.

Method used

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  • Method for synthesizing pramlintide
  • Method for synthesizing pramlintide

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Embodiment 1

[0025] A method for synthesizing pramlintide, comprising the steps of:

[0026] Step 1: Carry out fragment coupling reaction on the Rink Amide MBHA resin with a substitution degree of 0.25-0.40mmol / g; wherein, considering the synthetic pramlintide fragment 1 in step 2, which has a length of 31 amino acids, the selected Rink AmideMBHA resin replaces It is advisable that the concentration range is 0.25-0.40mmol / g.

[0027] Step 2: Synthesis of pramlintide fragment 1: Fmoc-Tyr(tBu)-OH is sequentially coupled from the C-terminus to the N-terminus until Fmoc-Cys(Trt)-OH at the 7th position of the N-terminus, and the Fmoc protecting group is removed; wherein, The amino acids used in the synthesis are all amino acids protected by Fmoc at the N-terminal, the Cys side chain is protected by Trt, the Asn side chain is protected by Trt, the Thr side chain is protected by tBu, the Gln side chain is protected by Trt, the Arg side chain is protected by Pbf, and the His side chain is protecte...

Embodiment 2

[0053] Step 1: Perform fragment coupling reaction on Rink Amide MBHA resin with a substitution degree of 0.25-0.40 mmol / g.

[0054]Step 2: Synthesis of pramlintide fragment 1: Fmoc-Tyr(tBu)-OH is sequentially coupled from the C-terminus to the N-terminus until Fmoc-Cys(Trt)-OH at the 7th position of the N-terminus, and the Fmoc protecting group is removed; wherein, The amino acids used in the synthesis are all amino acids protected by Fmoc at the N-terminal, the Cys side chain is protected by Trt, the Asn side chain is protected by Trt, the Thr side chain is protected by tBu, the Gln side chain is protected by Trt, the Arg side chain is protected by Pbf, and the His side chain is protected by Pbf. The side chain is protected by Trt, the Ser side chain is protected by tBu, and the Tyr side chain is protected by tBu; among them, the N-terminal 28 and 29 use the dipeptide amino acid Fmoc-Pro-Pro-OH, and the N-terminal 24 and 25 use the dipeptide amino acid Fmoc -Gly-Pro-OH, N-ter...

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Abstract

The invention discloses a method for synthesizing pramlintide, which comprises the following steps: synthesizing pramlintide fragments 1 and 2, preparing hydrazide 2cl resin with substitution degree of 0.5-0.8 mmol / g, respectively cracking the pramlintide fragment 1 and the pramlintide fragment 2, synthesizing crystalline pramlintide linear peptide, and oxidizing the crystalline pramlintide linearpeptide; the long peptide is synthesized by adopting an Fmoc solid phase method and a hydrazide method; according to the present invention, the dipeptide fragment is subjected to the fragment coupling reaction while DMSO oxidation is used, such that the method has characteristics of high synthesis efficiency, high yield, low cost and the like, is suitable for large-scale production, has considerable economic and practical values, and further has wide application prospects in the field of polypeptide drug design synthesis.

Description

technical field [0001] The invention relates to the technical field of chemical engineering, in particular to a method for synthesizing pramlintide, in particular to a solid-phase synthesis method for a hypoglycemic polypeptide drug pramlintide. Background technique [0002] Pramlintide is a polypeptide drug for treating diabetes, which has good effect and few side effects, and has a good market prospect. [0003] The Chinese preparation name of Pramlintide is Pramlintide Acetate, the polypeptide sequence is: KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-NH2 (S-S), the English name is: Pramlintide, molecular formula: C171H267N51O53S2, molecular weight: 3949.47, CAS accession number: 196078-30-5. [0004] In the synthesis process of pramlintide, there are many introductions of disulfide bond ring formation, and there are also many reports on the oxidation of pramlintide. However, in actual production, the oxidation process of pramlintide has brought great trouble to the production. ...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07K14/575C07K1/06C07K1/16A61P3/10
CPCC07K14/575A61P3/10Y02P20/55
Inventor肖攀沈永刚谢振亮程益明沈永良郑远鹏沈银超
OwnerHANGZHOU GOTOP BIOTECH