Branched and degradable polyethylene glycol derivative

Patent metadata

Field	Value
Publication number	US-12497508-B2
Application number	US-202017599163-A
Country	US
Kind code	B2
Filing date	Mar 26, 2020
Priority date	Mar 29, 2019
Publication date	Dec 16, 2025
Grant date	Dec 16, 2025

Abstract

An intracellularly degraded branched and degradable polyethylene glycol derivative represented by the following formula (1): wherein each symbol is as defined in the present specification, that is used for modifying bio-related substances is provided by the present invention.

First claim

The invention claimed is:

1 . A degradable polyethylene glycol derivative represented by the following formula (1):

wherein
n is 45-950,
W is an oligopeptide consisting of 5 to 47 residues and having a symmetrical structure centered on glutamic acid of formula w1, w2, or w3:

wherein Glu is a glutamic acid residue and Z is a degradable oligopeptide selected from the group consisting of glycine-phenylalanine-leucine-glycine (SEQ ID NO: 1), glycine-glycine-phenylalanine-glycine (SEQ ID NO: 2), glycine-phenylalanine-glycine, glycine-leucine-glycine, valine-citrulline-glycine, valine-alanine-glycine, and phenylalanine-glycine,
a is 2-8,
X is a functional group capable of reacting with a bio-related substance, and
L 1 and L 2 are each independently a divalent spacer.

2 . The degradable polyethylene glycol derivative according to claim 1 , wherein the total molecular weight is not less than 20,000 Daltons.

3 . The degradable polyethylene glycol derivative according to claim 1 , wherein L 1 is a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, or a urea bond; or an alkylene group optionally comprising a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, or a urea bond.

4 . The degradable polyethylene glycol derivative according to claim 1 , wherein L 2 is an alkylene group; or an alkylene group comprising at least one bond and/or group selected from the group consisting of a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, and a urea bond.

5 . The degradable polyethylene glycol derivative according to claim 1 , wherein X is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxide group, a maleimide group, a substituted maleimide group, a vinylsulfonyl group, an acrylic group, a substituted sulfonate group, a sulfonyl oxy group, a carboxyl group, a mercapto group, a pyridyldithio group, an α-halo acetyl group, an alkylcarbonyl group, an iodoacetamide group, an alkenyl group, an alkynyl group, a substituted alkynyl group, an amino group, an oxyamino group, a hydrazide group and an azide group.

6 . The degradable polyethylene glycol derivative according to claim 2 , wherein L 1 is a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, or a urea bond; or an alkylene group optionally comprising a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, or a urea bond.

7 . The degradable polyethylene glycol derivative according to claim 6 , wherein L 2 is an alkylene group; or an alkylene group comprising at least one bond and/or group selected from the group consisting of a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, and a urea bond.

8 . The degradable polyethylene glycol derivative according to claim 7 , wherein X is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxide group, a maleimide group, a substituted maleimide group, a vinylsulfonyl group, an acrylic group, a substituted sulfonate group, a sulfonyl oxy group, a carboxyl group, a mercapto group, a pyridyldithio group, an α-halo acetyl group, an alkylcarbonyl group, an iodoacetamide group, an alkenyl group, an alkynyl group, a substituted alkynyl group, an amino group, an oxyamino group, a hydrazide group and an azide group.

9 . The degradable polyethylene glycol derivative according to claim 3 , wherein L 2 is an alkylene group; or an alkylene group comprising at least one bond and/or group selected from the group consisting of a carbonyl group, a urethane bond, an amide bond, an ether bond, a thioether bond, a secondary amino group, and a urea bond.

10 . The degradable polyethylene glycol derivative according to claim 9 , wherein X is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxide group, a maleimide group, a substituted maleimide group, a vinylsulfonyl group, an acrylic group, a substituted sulfonate group, a sulfonyl oxy group, a carboxyl group, a mercapto group, a pyridyldithio group, an α-halo acetyl group, an alkylcarbonyl group, an iodoacetamide group, an alkenyl group, an alkynyl group, a substituted alkynyl group, an amino group, an oxyamino group, a hydrazide group and an azide group.

Assignees

• Nof Corp
• Tokyo Inst Tech

Inventors

• Yoshioka Hiroki
• Osakama Kazuki
• HAMURA Mika
• Inaba Takanori
• Nishiyama Nobuhiro
• Matsui Makoto
• Takemoto Hiroyasu
• Nomoto Takahiro
• Sun Xiaohang

Classifications

• C08L2201/06

  Biodegradable · CPC title

• C08L101/16 Primary

  the macromolecular compounds being biodegradable · CPC title

• C08G65/3332

  containing carboxamide group · CPC title

• C08L71/02 Primary

  Polyalkylene oxides · CPC title

• C08G65/334

  containing sulfur · CPC title