Glycopeptide compositions

Patent metadata

Field	Value
Publication number	US-9820986-B2
Application number	US-7197505-A
Country	US
Kind code	B2
Filing date	Mar 4, 2005
Priority date	Mar 4, 2005
Publication date	Nov 21, 2017
Grant date	Nov 21, 2017

Abstract

The invention include glycopeptides having a glycoside and a peptide covalently bound through an amide bond. The glycopeptides may also include a diagnostic or therapeutic agent bound to the glycopeptide. A metal, such as a radionuclide, may also be chelated to the glycopeptide. Specific embodiments of the invention relate to glycopeptides made of chitosan covalently bound to a poly(amino acid) such as poly(glutamic acid) or poly(aspartic acid). Diagnostic agents conjugated to the glycopeptide may facilitate imaging. Specific therapeutic agents that may be conjugated to the glycopeptide include anticancer drugs, rheumatoid arthritis drugs, anticoagulants, anti-angiogenesis drugs, apoptosis drugs, osteoporosis drugs, steroids, and anti-inflammatory drugs. Some agents, such as radionuclides, may have both diagnostic and therapeutic effects. The glycopeptides may be made by combining a glycoside and a peptide in the presence of a carbodiimide and an acid group activator to form an amide bond between the glycoside and the peptide.

First claim

The invention claimed is:

1. A glycopeptide targeting a tumor tissue comprising:
a chitosan moiety;
a poly(glutamic acid) or poly(aspartic acid) moiety comprising carboxyl groups;
a therapeutic agent; and
a metal,
wherein the chitosan moiety is covalently bonded to the poly(glutamic acid) or poly(aspartic acid) moiety via an amide bond,
wherein the therapeutic agent is conjugated to the chitosan through a carboxylic acid via a peptide bond linkage, and
wherein the metal is a radionuclide and is conjugated to the carboxyl groups of the poly(glutamic acid) or poly(aspartic acid);
wherein the glycopeptide exhibits preferential affinity for a tumor tissue relative to bone tissue.

2. The glycopeptide of claim 1 , wherein the glycopeptide comprises the poly(glutamic acid) or poly(aspartic acid) moiety in an amount of from about 5% to about 50% by weight of the glycopeptide.

3. The glycopeptide of claim 1 , wherein the chitosan moiety has a molecular weight of from about 3,000 daltons to about 10,000 daltons, and wherein the poly(glutamic acid) or poly(aspartic acid) moiety has a molecular weight of from about 750 daltons to about 3,000.

4. The glycopeptide of claim 1 , wherein the glycopeptide has a molecular weight of at least about 10,000 daltons.

5. The glycopeptide of claim 1 , wherein the therapeutic agent is selected from the group consisting of: anticancer drugs, rheumatoid arthritis drugs, anticoagulants, anti-angiogenesis drugs, apoptosis drugs, steroids, anti-inflammatory drugs, and any combinations thereof.

6. The glycopeptide of claim 1 , wherein the therapeutic agent comprises methotrexate.

7. The glycopeptide of claim 1 , wherein the metal is selected from the group consisting of: Tc-99m, Cu-60, Cu-61, Cu-62, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-186, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Gd-157, Bi-212, and Bi-213, and any combinations thereof.

8. The glycopeptide of claim 1 , wherein the glycopeptide comprises the therapeutic agent in an amount of from about 10% to about 60% by weight of the glycopeptide.

9. The glycopeptide of claim 1 , wherein the chitosan moiety targets vascular endothelial cells and the poly(glutamic acid) or poly(aspartic acid) moiety targets cancer cells.

10. A method of producing a glycopeptide comprising:
combining chitosan and poly(glutamic acid) or poly(aspartic acid) in the presence of a carbodiimide and an acid group activator to form an amide bond between the chitosan and poly(glutamic acid) or poly(aspartic acid); and
forming an amide or ester bond between the chitosan or poly(glutamic acid) or poly(aspartic acid) and a diagnostic or therapeutic agent.

11. The method of claim 10 , further comprising conjugating a chelating agent and a metal to the chitosan or poly(glutamic acid) or poly(aspartic acid).

12. A glycopeptide targeting a tumor tissue comprising:
a chitosan moiety;
a poly(glutamic acid) or a poly(aspartic acid) moiety comprising carboxyl groups; and
a metal,
wherein the chitosan moiety is covalently bonded to the poly(glutamic acid) or poly(aspartic acid) moiety via an amide bond,
wherein the metal is a radionuclide and is conjugated to the carboxyl groups of the poly(glutamic acid) or poly(aspartic acid), and wherein said glycopeptide exhibits preferential affinity for a tumor tissue relative to bone tissue.

13. The glycopeptide of claim 12 , wherein the glycopeptide comprises the poly(glutamic acid) or poly(aspartic acid) moiety in an amount of from about 5% to about 50% weight of the glycopeptide.

14. The glycopeptide of claim 12 , wherein the chitosan moiety has molecular weight of from about 3,000 daltons to about 10,000 daltons, and wherein the poly(glutamic acid) or poly(aspartic acid) moiety has a molecular weight of from about 750 daltons to about 3000.

15. The glycopeptide of claim 12 , wherein the glycopeptide has a molecular weight of at least about 10,000 daltons.

16. The glycopeptide of claim 12 , wherein the metal is selected from the group consisting of: Tc-99m, Cu-60, Cu-61, Cu-62, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-186, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Gd-157, Bi-212, and Bi-213, and any combinations thereof.

Assignees

• Wei I-Chien
• Yang David J
• Yu Dong-Fang
• Taiwan Hopaz Chems Mfg Co Ltd
• Univ Texas

Inventors

• Wei I-Chien
• Yang David J
• Yu Dong-Fang

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title