Long-acting Exendin-4 analogue and application thereof

An analogue, exenatide technology, applied in the field of long-acting exenatide analogues, can solve the problems of prolonging the half-life of GLP-1, and achieve the effects of prolonging the biological half-life, improving efficiency, and avoiding local itching

Inactive Publication Date: 2016-09-14
CHINA PHARM UNIV
View PDF6 Cites 13 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since the peptide is also rapidly filtered and eliminated in the kidney, the degr

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
  • Long-acting Exendin-4 analogue and application thereof
  • Long-acting Exendin-4 analogue and application thereof
  • Long-acting Exendin-4 analogue and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0062] Example 1

[0063]

[0064] Microwave promoted solid phase synthesis

[0065] (1) Cysteine ​​synthesis with side chain modification

[0066] Weigh 0.21g of Fmoc-Cys-OH, dissolve it in DCM, add 0.12g of N-octylmaleimide, 3ul DIEA as a catalyst, and stir at room temperature for 4 hours. After the reaction is monitored by the thin-layer plate, the reaction The solution was concentrated under reduced pressure and separated by column chromatography to obtain 0.27 g of the product with a yield of 79%.

[0067] MS(70eV)m / z: 575.6([M+Na] + ).

[0068] (2) Swelling of resin

[0069] Weigh 50mg of Fmoc-Rink amide-MBHA Resin (substitution amount 0.4mmol / g), swell with 7mL DCM for 30min, filter to remove DCM, swell with 10mL NMP for 30min, and finally rinse with NMP, DCM, NMP 7mL respectively.

[0070] (3) Microwave promotes the removal of Fmoc protecting group

[0071] Put the swollen resin into the reactor, add 7 mL of 25% piperidine / NMP(V / V) solution containing 0.1M HOBT, and react in a mic...

Example

[0084] Examples 2-9

[0085] According to the method described in Example 1, the Exendin-4 analogs of Examples 2-9 were synthesized according to the corresponding sequences, and their molecular weights were confirmed by electrospray mass spectrometry (ESI-MS).

Example Embodiment

[0086] Example 2

[0087]

[0088] The theoretical relative molecular mass is 4426.8. ESI-MS m / z: found[M+3H] 3+ 1476.6, [M+4H] 4+ 1107.7; calu[M+3H] 3+ 1476.8, [M+4H] 4+ 1107.9.

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 a long-acting Exendin-4 analogue and a synthesis method thereof. Exendin-4 is transformed to obtain the Exendin-4 analogue having longer pharmacological action time, synthesis of a target polypeptide is rapidly achieved by a microwave-promoted solid phase synthesis method, and a crude product is purified and freeze-dried to obtain the Exendin-4 analogue.

Description

technical field [0001] The invention relates to long-acting exenatide (Exendin-4) analogs in the field of diabetes treatment and applications thereof. Background technique [0002] Diabetes is the third chronic non-communicable disease that seriously threatens human health after tumors and cardiovascular diseases. Currently, there are about 300 million diabetics in the world, which is expected to increase to 500 million by 2025. Clinically, intensive insulin therapy is used to delay the progression of diabetes. Insulin therapy can reverse the damage of pancreatic β-cell function to a certain extent while lowering blood sugar. However, there is a risk of hypoglycemia with insulin. Affected by factors such as dose size, injection site, injection route, individual differences or not eating after injection, if insulin is used carelessly, severe hypoglycemia side effects will occur. [0003] Glucagon-like peptide-1 (GLP-1) is a glucose-dependent incretin hormone. GLP-1 stimula...

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
IPC IPC(8): C07K14/575A61K38/22A61P3/10
CPCC07K14/57563A61K38/00
Inventor 黄文龙钱海孙李丹蔡星光韩京褚莹莹周洁
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap