Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Disulfide cross-linked glycoprotein hormone analogs, their preparation and use

A technology for glycoprotein hormones and analogs, which is applied in the field of disulfide-bonded glycoprotein hormone analogs and their preparation and application, and can solve problems such as reducing hormone activity

Inactive Publication Date: 2007-02-28
MERCK SERONO SA
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is also a review of these intersubunit disulfide bonds in Han et al. (1996), but the literature reports that the introduction of such disulfide bonds may reduce hormone activity

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
  • Disulfide cross-linked glycoprotein hormone analogs, their preparation and use
  • Disulfide cross-linked glycoprotein hormone analogs, their preparation and use
  • Disulfide cross-linked glycoprotein hormone analogs, their preparation and use

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0086] Although derivatives are usually prepared by first synthesizing a lead molecule and then derivatizing, derivatives can also be prepared directly. However, the implicit meaning of the term "derivative" is that derivatives are obtained with available techniques by modifying the lead molecule, even if that is not the preferred method of production.

[0087] Modifications to proteins can be divided into the following categories:

[0088] Advantageous - These modifications enhance the utility of the protein for a particular purpose.

[0089] Neutral—These modifications neither enhance nor impair the utility of the protein for a particular purpose.

[0090] Disadvantageous - These modifications impair (but do not necessarily eliminate) the utility of the protein for a particular purpose.

[0091] Inactivation - These modifications eliminate the utility of a specific purpose protein.

[0092] Tolerable - These modifications are favorable, neutral, or unfavorable, but are no...

Embodiment 1

[0254] Example 1: hCG stabilized by intersubunit disulfide bonds between cysteine ​​nodules: hCG(α31-β37)

[0255] Following the criteria for intersubunit disulfide cross-links, the data in Table 1B suggest that if a free cysteine ​​is generated at residue 31 of the α subunit and replaced by a cysteine ​​at Tyr37 in the β subunit, then there is It is possible to make hCG analogs stabilized by intersubunit disulfide bonds between cysteine ​​nodules. This is achieved by making hCG beta subunit analogs in which Tyr37 is replaced by cysteine ​​and human alpha subunit analogs in which Cys7 is replaced by Ser. The latter change disrupts the disulfide bond normally seen between amino acids Cys7 and Cys31 within the α subunit, leaving a free α-subunit cysteinergic at residue 31 and an imported half-cysteine ​​at residue 37 of the β-subunit. Cystine forms disulfide bonds. When each of these subunit constructs is expressed in cultured mammalian cells, the cysteine ​​at residue 31 of t...

Embodiment 2

[0277] Example 2: Multifunctional Glycoprotein Hormone Analogs Stabilized by Intersubunit Disulfide Bonds Located Between the Cysteine ​​Knuckles in the α and β Subunits

[0278] The locus tether is known to affect the receptor binding activity of hCG (Campbell et al., 1991; Moyle et al., 1994; Han et al., 1996). Replacement of hCGβ subunit amino acid residues 101-109 by their hFSH counterparts (i.e., hFSHβ subunit residues 95-103) resulted in a greatly increased FSH activity of the analog without compromising its LH activity (Moyle et al., 1994; Han et al., 1996). In fact, this substitution also enhanced the TSH activity of hCG (Campbell et al., 1997), even though it did not introduce any specific residues seen in hTSH. Studies of the effect of intersubunit disulfide bonds on the activity of related multifunctional analogs show how specific disulfide bonds affect the activity of luteinizing hormone, follicle-stimulating hormone, and thyrotropin. This example describes how i...

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 analogs of glycoprotein hormones with an intersubunit disulfide cross-link and their preparation and use. Corresponding DNA sequences and host cells, as well as pharmaceutical compositions are also disclosed.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of June 25, 1998, an application number of CN 98807811.2, and an invention title of "disulfide bond cross-linked glycoprotein hormone analogue and its preparation and application". technical field [0002] The present invention relates to analogs of glycoprotein hormones and their preparation and application. More specifically, the present invention relates to disulfide cross-linked glycoprotein hormone analogs and their preparation and use. Background technique [0003] Glycoprotein hormones include chorionic gonadotropin (CG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). These hormones in humans are called human chorionic gonadotropin (hCG), human luteinizing hormone (hLH), human follicle stimulating hormone (hFSH), human thyroid stimulating hormone (hTSH). These hormones play an important role in gonadal and ...

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 Patents(China)
IPC IPC(8): C07K14/59A61K38/24A61P15/08A61P15/18C12N15/09C12N15/16C12N15/79A61K38/00A61K38/22C12N5/10C12P21/00
CPCC07K14/59A61K38/00A61P15/08A61P15/18A61P5/06C12N15/11A61K38/27
Inventor W·R·莫伊尔
Owner MERCK SERONO SA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com