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Glucose-sensitive peptide hormones

A technology for glucose and peptide hormones, applied in the field of pharmaceutical or veterinary compositions, drugs for treating diabetes, and reagents for inactivating or inhibiting the activity of peptide hormones, and can solve problems such as changing the activity of peptide hormones

Inactive Publication Date: 2019-08-02
GUBRA APS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0036] The peptide conjugates according to the present invention address and solve the problem of altering the hormonal activity of peptide hormones in response to fluctuating carbohydrate concentrations in the body by establishing homeostasis to release active peptide hormones in response to elevated glucose concentrations in vivo

Method used

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  • Glucose-sensitive peptide hormones
  • Glucose-sensitive peptide hormones
  • Glucose-sensitive peptide hormones

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0166] Example 1 illustrates the synthesis of exemplary hydrolyzable linker (L) molecules.

Embodiment 2

[0167] Example 2 illustrates a method for forming a linker (L) with a handle ready for grafting peptide (P) and inhibitor (I).

Embodiment 3

[0168] Example 3 illustrates the synthesis of a linker attached to an inhibitor (I). In this example, the inhibitor or inactivator complex (I) is a C18 fatty acid, which does not itself inhibit the activity of the peptide (see Example 4), but which is known to bind albumin in vivo. Thus, inactivation in vivo is ultimately achieved by inhibitor binding and aggregation of the conjugate to albumin.

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Abstract

The present invention relates to a conjugate of the formula P-L-I, wherein P is a peptide hormone effecting the metabolism of carbohydrates in vivo, L is a hydrolysable linker molecule consisting of Lp and Li, and I is a molecule capable of inhibiting the effect of the peptide hormone P on the metabolism of carbohydrates in vivo. Under in vivo conditions, the conjugate is the major compound. Whenthe concentration of glucose increases in vivo, the concentration of the peptide hormone effecting the metabolism of carbohydrates in vivo also increases.

Description

technical field [0001] The present invention relates to glucose-responsive peptide conjugates comprising a peptide hormone that affects carbohydrate metabolism in vivo, and an agent that inactivates or inhibits the activity of the peptide hormone (or an agent that promotes the activity of the peptide hormone) conjugated via a hydrolyzable linker molecule. inactivating or inhibiting reagents). [0002] Furthermore, the present invention relates to the use of the glucose-responsive peptide conjugate as a medicament, in particular as a medicament for the treatment of diabetes. [0003] The peptide hormone part of the conjugate according to the invention is inactive in the conjugate due to the presence of an inhibitor which inactivates or inhibits the activity of the peptide hormone. [0004] The hydrolyzable linker of the conjugate promotes the homeostasis of the peptide hormone, inhibitor and conjugate in vivo. [0005] The invention also relates to a pharmaceutical or veterin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61P3/10
CPCA61K47/542A61P3/10A61K38/28A61K47/54A61K47/545C07K14/62C07K19/00A61K47/64
Inventor K·J·延森C·S·马德森K·M·S·曼纳斯泰特E·M·贝克S·L·佩德森J·杰尔辛N·弗朗
Owner GUBRA APS