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Xenopus laevis glucagon-like peptide-1 analogue and application thereof

A glucagon, Xenopus technology, applied in glucagon, hormone peptides, specific peptides, etc., can solve problems such as short half-life

Pending Publication Date: 2021-04-30
XUZHOU NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, natural GLP-1 has limitations, that is, its half-life is extremely short, and it will be degraded by dipeptidyl peptidase (DPP-IV) after 2 to 3 minutes of secretion, even if GLP-1 is given exogenously, it is also very fast Will be degraded by DPP-IV

Method used

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  • Xenopus laevis glucagon-like peptide-1 analogue and application thereof
  • Xenopus laevis glucagon-like peptide-1 analogue and application thereof
  • Xenopus laevis glucagon-like peptide-1 analogue and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037]

[0038] (1) Swelling of the resin

[0039] Weigh 0.262g (0.1mmol) of Rink Amide MBHA resin with a loading capacity of 0.382mmol / g, put it into a 25mL reactor, wash the resin once with 7mL of DCM and methanol alternately, and wash the resin twice with 7mL of DCM, The resin was then swollen with 7 mL of DCM for 1 h, and finally the resin was washed 3 times with 7 mL of DMF.

[0040] (2) Removal of resin Fmoc protecting group

[0041] Transfer the swollen resin to a peptide synthesizer, add 7mL 20% piperidine / DMF to react at room temperature for 5min, filter off the deprotection solution, wash the resin once with 7mL DMF, then add 7mL 20%piperidine / DMF to deprotect and wash the resin for 15min, Finally, the resin was washed 4 times with 7 mL of DMF, 1.5 min each time, to obtain the Rink resin from which the Fmoc protecting group was removed.

[0042] (3) Synthesis of Fmoc-Lys-Rink amide-MBHA Resin

[0043] Weigh Fmoc-Lys(Boc)-OH (0.4mmol), dissolve it with 3mL 10% D...

Embodiment 2～19

[0053] According to the method described in Example 1, the Xenopus laevis glucagon-like peptide-1 (XenGLP-1) analogues of Examples 2 to 30 were synthesized according to the corresponding sequences and side chains, and the respective peptides were confirmed by ESI-MS. molecular weight.

Embodiment 2

[0055]

[0056] The theoretical relative molecular mass is 3838.3. ESI-MS m / z:calu[M+3H] 3+ 1290.4,[M+4H] 4+ 968.1;found[M+3H] 3+ 1290.6,[M+4H] 4+ 968.5.

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Abstract

The invention discloses a xenopus laevis GLP-1 analogue as well as a synthesis method and application thereof, and the xenopus laevis GLP-1 analogue with higher hypoglycemic activity and longer pharmacological action time is obtained by performing structural modification on a side chain and a C terminal of xenopus laevis GLP-1. The xenopus laevis GLP-1 analogue has the advantages that the biological activity is obviously improved, and the very strong long-acting blood glucose reducing and weight losing effects are realized.

Description

[0001] The present invention is a divisional application, the application number of the original application is 2017111943239, the application date is November 24, 2017, and the name of the invention is Xenopus laevis GLP-1 analog and its use. technical field [0002] The invention relates to the field of biomedicine, in particular to a class of Xenopus glucagon-like peptide-1 analogs and applications thereof. Background technique [0003] Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia caused by genetic and environmental factors. A series of metabolic disorders such as sugar, protein, fat, water and electrolytes are caused by relative or absolute deficiency of insulin secretion; or defects in insulin action. Persistent hyperglycemia is the basic feature. Prolonged illness can cause damage to multiple systems, leading to chronic complications in the eyes, kidneys, nerves, cardiovascular and cerebrovascular organs, and lower lim...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/605A61K38/26A61P3/10A61P3/04A61P3/06A61P3/00A61P25/00A61P9/12A61P9/10A61P9/00A61P1/14A61P1/00
CPCC07K14/605A61K38/00A61P3/10A61P3/04A61P3/06A61P3/00A61P25/00A61P9/12A61P9/10A61P9/00A61P1/14A61P1/00
Inventor 韩京
Owner XUZHOU NORMAL UNIVERSITY