Supercharge Your Innovation With Domain-Expert AI Agents!

Sulfur-containing polyethylene glycol resins for polypeptide synthesis

A technology for synthesis of polyethylene glycol and peptides, which is applied in the preparation method of peptides, peptides, organic chemistry, etc., can solve the problems of polyethylene glycol disorder, large swelling, unevenness, etc., and achieve stable chemical properties and quality , The effect of increasing the coupling speed

Pending Publication Date: 2021-05-28
苏州金顶生物有限公司 +1
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] In the third method, when the alkyl dianhydride reacts with the two-terminal amino polyethylene glycol, it is easy to obtain a single-terminal carboxyl polyethylene glycol and a two-terminal carboxyl polyethylene glycol. The two cannot be separated, and will form in the subsequent synthesis. Complex components, impurity components also react with the amine groups of the resin, resulting in poor quality polyethylene glycol resin
The commercialized TentaGel resin has a short PEG chain, and the length of the PEG on the link is uneven, resulting in unstable quality of the synthesized peptide
PEG as the matrix generally has the defects that the swelling property is too strong and it is not easy to wash, and the resin expands too much and is not easy to filter when TFA cuts peptides.
[0024] The above-mentioned resins have problems such as complex production process of modified polyethylene glycol, intolerant of organic bases, messy or uneven polyethylene glycol on the surface of the resin, excessive swelling, and inconvenient operation.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Sulfur-containing polyethylene glycol resins for polypeptide synthesis
  • Sulfur-containing polyethylene glycol resins for polypeptide synthesis
  • Sulfur-containing polyethylene glycol resins for polypeptide synthesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0191] Example 1H 2 N-PEG (60～80) -CH 2 CH 2 CH 2 -S-CH 2 CH 2 -COOH (compound 7, R 3 =H)

[0192] 1) HO-PEG (60～80) -CH 2 CH 2 CH 2 -S-CH 2 CH 2 -COOtBu synthesis

[0193] Dissolve 840g (about 0.24mol) of APEG3500 in 7L of 1,4-dioxane, under nitrogen protection, add 88.9g (0.6mol) of tert-butyl 2-mercaptoacetate, raise the temperature to 55°C, and add 9.4g of (0.03mol) AIBN, when the temperature stabilized to 55°C, remove the nitrogen protection, react at 55°C for 13h, and MS detected that the reaction was complete.

[0194] About 4L of 1,4-dioxane was removed by rotary evaporation under reduced pressure, 10L of water was added, and petroleum ether (5L×3) was used to extract a large amount of unreacted tert-butyl 2-mercaptoacetate. The aqueous layer was adjusted to pH=4 with 40% phosphoric acid (a small amount of acid is enough), extracted with dichloromethane (5L*2), washed once with water, dried with anhydrous sodium sulfate, and evaporated to dryness under r...

Embodiment 2

[0204] Example 2 Me-HN-PEG (8～12) -CH 2 CH 2 CH 2 -S-CH 2 CH 2 COOH (compound 9, R 3 = Hydrogen, R 5 = methyl)

[0205] 1) Me-NH-PEG (8～12) -CH 2 CH 2 CH 2 -S-CH 2 CH 2 -COOtBu

[0206] 70g (0.1mol) Tos-O-PEG (8～12) -CH 2 CH 2CH 2 -S-CH 2 CH 2 -COOtBu was dissolved in 400ml of tetrahydrofuran, cooled to -60°C, and 100ml of 3M methylamine tetrahydrofuran solution was added dropwise. After the addition was complete, it was kept at -60°C and stirred for 3 hours. The solvent was evaporated to dryness under reduced pressure to obtain a pale yellow oil, 400ml of water was added to dissolve the oil, the aqueous phase was extracted with ethyl acetate (200ml×3), the acetic acid was washed once with 200ml of saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. On drying, 53 g of a yellow oil were obtained.

[0207] 2) Me-NH-PEG (8～12) -CH 2 CH 2 CH 2 -S-CH 2 CH 2 -COOH

[0208] 35g (52mmol) NH 2 -PEG (20～30) -CH 2 CH...

Embodiment 3

[0211] NH 2 -CH 2 -CH 2 -S-CH 2 CH 2 CH 2 -PEG(30~40)-CH 2 CH 2 COOH (Compound 16, R1=H, R2=H)

[0212] 1) Synthesis of Boc-NH-CH2-CH2-S-CH2CH2CH2-PEG(30~40)-OH (compound 14)

[0213] Dissolve 150g (about 0.1mol) of APEG1500 in 600ml of 1,4 dioxane, under nitrogen protection, add 106g (0.6mol) of Boc-cysteamine (compound 13), heat up to 55°C, add 3.3g of ( 0.02mol) AIBN, when the temperature stabilized to 55°C, remove the nitrogen protection, react at 55°C for 9h, and MS detected that the reaction was complete.

[0214] Remove about 400ml of 1,4-dioxane by rotary evaporation under reduced pressure, add 400ml of water, and extract a large amount of unreacted Boc-cysteamine with petroleum ether (400ml×3). The aqueous layer was adjusted to pH=4 with 40% phosphoric acid, extracted with dichloromethane (300ml×2), washed once with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to obtain Boc-NH-CH 2 -CH 2 -S-CH 2 CH 2 CH 2 -...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to sulfur-containing polyethylene glycol resins for polypeptide synthesis. Polyethylene glycol monoallyl ether reacts with a sulfhydryl compound containing amido or carboxyl to obtain polyethylene glycol containing sulfur, and meanwhile, the amido or carboxyl is introduced into the polyethylene glycol, so that modified polyethylene glycol is very conveniently introduced into the resin, and the sulfur-containing polyethylene glycol resins with different effects are obtained. The sulfur-containing polyethylene glycol resins can be used for solid-phase polypeptide synthesis, and are especially suitable for continuous flow solid-phase polypeptide synthesis.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to the preparation and application of sulfur-containing polyethylene glycol resin. Background technique [0002] Merrifield et al. reported the concept of solid-phase peptide synthesis as early as the 1960s, cross-linking styrene into different types of chloromethylated polystyrene [0003] [Wu M, Yang G, Chen Z. Polymer supported peroxodisulfate: A mild and clean oxidation of organic compounds under nonaqueous and aprotic conditions. React Funct Polym, 2000, 44:97—100; Hari A, Miller BL. Exploiting differences in solution vs solid -supported reactivity for the synthesis of sulfonic acid derivatives. Org Lett, 1999, 1:2109—2111] as a carrier resin for solid phase synthesis of polypeptides (Merrifield resin, as shown below). Since then, polymeric solid supports have become more and more common in the synthesis and purification of products. [0004] [0005] Structure...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C08G65/338C08G65/337C08G65/335C08G65/334C08G65/332C08G65/325C07K1/04
CPCC08G65/3344C08G65/338C08G65/325C08G65/335C08G65/337C08G65/3322C07K1/042Y02P20/55
Inventor 向双春高峰李云平
Owner 苏州金顶生物有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com