Cationic polymers with D-fructose substituents

Patent metadata

Field	Value
Publication number	US-11530296-B2
Application number	US-201816495676-A
Country	US
Kind code	B2
Filing date	Mar 23, 2018
Priority date	Mar 23, 2017
Publication date	Dec 20, 2022
Grant date	Dec 20, 2022

Abstract

The invention relates to new cationic polymers conjugated with D-fructose, as a result of which they can selectively interact with specific structure elements on cell surfaces. The problem was that of creating novel, biocompatible, easy-to-produce, D-fructose-conjugated cationic polymers that have a higher selectivity with respect to certain cell types. To solve this problem, the invention proposes cationic polymers with covalently bonded D-fructose of general formula (I) with the following components: a) cationic polymer: macromolecular compounds of n repeat units with one or more positive charges; b) linker: a unit that links the cationic polymer with D-fructose or derivatives of D-fructose by means of any alkyl or aryl group, any alkenyl or alkinyl group, an ether, thioether or amine, an ester, amide or other carboxylic acid derivative, a heterocycle (e.g. triazole or m maleimide), a disulphide, an imine or an imide; c) D-fructose: one or more D-fructoses or D-fructose derivatives in an open-chain, furanoid or pyranoid structure, not glycosidically linked via one of the five possible carbon atoms (1, 3, 4, 5, 6).

First claim

What is claimed is:

1. A cationic polymer having covalently bonded D-fructose of the general formula (I) comprising:
a macromolecular compound of n repeating units having one or more positive charges;
one or more D-fructose or D-fructose derivative in open-chain, furanoid or pyranoid structure; and
a linker including one or more linking units linking the macromolecular compound to the one or more D-fructose or D-fructose derivative by an alkyl radical, or an aryl radical, or an alkenyl radical, or an alkynyl radical, or an ether, or a thioether, or an amine, or an ester, or an amide, or another carboxylic acid derivative, or a heterocycle, or a disulfide, or an imine, or an imide,

wherein the linker covalently links the one or more D-fructose or D-fructose derivative to the macromolecular compound, and the one or more D-fructose or D-fructose derivative is non-glycosidically linked via its carbon atom C1, C3, C4, C5, or C6 to the linker.

2. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer comprises functional groups which have positive charges under appropriate conditions.

3. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer comprises functional groups which can carry positive charges at different positions once or several times in the cationic polymer.

4. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer is a homopolymer or a copolymer.

5. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer is linear or branched.

6. The cationic polymer of claim 5 , wherein the cationic polymer is a branched polymer, the branched polymer being a star polymer, a brush polymer, or a comb polymer.

7. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the one or more D-fructose or D-fructose derivative are bonded to individual, a plurality of or all repeating units of the macromolecular compound via the linker.

8. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the one or more D-fructose in addition to free OH groups further comprises a substituent on the carbon atoms 1, 2, 3, 4, 5 and/or 6.

9. The cationic polymer having covalently bonded D-fructose according to claim 1 , further comprising a biologically active material selected from the group of nucleic acids, the biologically active material being bonded electrostatically and/or covalently.

10. The cationic polymer having covalently bonded D-fructose according to claim 8 , wherein the nucleic acids are selected from the group of DNA, RNA, a ribosome and/or a DNA-RNA hybrid.

11. The cationic polymer of claim 10 , wherein the nucleic acids are double stranded or single stranded.

12. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer is adapted for a transport and a delivery of a biologically active material into a living cell.

13. The cationic polymer having covalently bonded D-fructose according to claim 1 , wherein the cationic polymer is adapted for a selective killing of certain cell types.

14. The cationic polymer of claim 1 , wherein the one or more D-fructose or D fructose derivative is linked via carbon atom C6 to the linker.

15. The cationic polymer of claim 1 , wherein a toxicity of the cationic polymer to cancer cells is greater than a toxicity of the cationic polymer to non-cancer cells.

16. The cationic polymer of claim 15 , wherein the cancer cells are breast cancer cells.

17. The cationic polymer of claim 15 , wherein the cancer cells are of cell line MDA-MB- 231 and the non-cancer cells are HUVEC and L929.

Assignees

• Univ Jena Friedrich Schiller

Inventors

• Gottschaldt Michael
• Proehl Michael
• Englert Christoph
• Schubert Ulrich Sigmar

Classifications

• A61K47/543

  Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine · CPC title

• C08G69/48 Primary

  Polymers modified by chemical after-treatment · CPC title

• A61K47/6455

  Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids · CPC title

• C08G73/0226

  Quaternisation of polyalkylene(poly)amines · CPC title

• C07H3/02

  Monosaccharides · CPC title