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

Transglutaminase mediated conjugation of growth hormone

A technology of glutamine and growth hormone, applied in the field of post-translational binding of growth hormone, can solve problems such as limiting connection points and restrictions

Inactive Publication Date: 2009-02-11
NOVO NORDISK AS
View PDF16 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this process limits the point of attachment of the C-terminal amino acid residue, which sometimes poses a serious limitation if the C-terminal residue is critical for the activity of the peptide

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
  • Transglutaminase mediated conjugation of growth hormone
  • Transglutaminase mediated conjugation of growth hormone
  • Transglutaminase mediated conjugation of growth hormone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0517] Embodiment 1. A method of covalently linking PEG to a polypeptide comprising at least one glutamine residue, said method comprising in one or more steps making said glutamine residue comprising a polypeptide represented by formula [I] Aminoamide residues

[0518]

[0519] where PP means that by removing -C(=O)-NH from the side chain of a glutamine residue present in the polypeptide 2 The obtained polypeptide group, with the nitrogen-containing nucleophile of formula [II]

[0520] h 2 N-D-R-X

[0521] [II]

[0522] Where D represents -O- or a single bond;

[0523] R for C 1-6 Alkylene, -(CH 2 ) 4 -CH(NH 2 )-CO-NH-CH 2 -, -(CH 2 ) 4 -CH(NHCOCH 3 )-CO-NH-CH 2 - or C 5-15 Heteroalkylene;

[0524] X stands for -O-NH 2 , aldehydes, ketones, or can be converted to -O-NH by further reactions 2 , potential groups of aldehydes or ketones;

[0525] Reaction in the presence of transglutaminase, thereby forming the transaminated polypeptide of formula [III]

[...

Embodiment approach 2

[0545] Embodiment 2. The method according to embodiment 1, wherein D represents -O-.

Embodiment approach 3

[0546] Embodiment 3. The method according to embodiment 1, wherein D represents a single bond.

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

A method for PEGylating growth hormone, said method comprising reacting growth hormone with an amine comprising nucleophile which further comprises a first functional group in the presence of TGase to form a transaminated growth hormone, followed by a reaction of said transaminated growth hormone with a PEG which has been functionalised with a second functional group, wherein said first and second functional groups are selected so that they react to form a covalent bond.

Description

field of invention [0001] The present invention relates to a novel method of post-translational conjugation of growth hormone in which transglutaminase is used to incorporate at specific positions on the peptide an attachment point whereby PEG can be selectively attached to the peptide. The conjugated growth hormones have altered properties and can thus be used in therapeutic applications. Background of the invention [0002] It is well known that the properties and properties of a peptide can be altered by attaching to the peptide appropriate groups that alter the properties of the peptide. Such conjugation typically requires some functional groups on the peptide to react with other functional groups on the conjugating group. Generally, amino groups such as the N-terminal amino group or the epsilon-amino group of lysine have been used in conjunction with a suitable acylating reagent. It is often desirable or even required to be able to control the conjugation reaction, ie...

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): A61K47/48C07K14/61A61K38/00A61K47/60
Inventor F·Z·多沃尔德N·L·约翰森L·F·伊弗森
Owner NOVO NORDISK AS
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