Glycopeptide compositions

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.

1 . A glycopeptide comprising:
 a glycoside moiety;   a peptide moiety; and   a diagnostic or therapeutic agent, wherein the glycoside moiety is covalently bonded via an amide bond to the peptide moiety and the diagnostic or therapeutic agent is conjugated to the peptide moiety.   
     
     
         2 . The glycopeptide of  claim 1 , further comprising a metal conjugated to the glycoside moiety. 
     
     
         3 . The glycopeptide of  claim 2 , wherein the diagnostic or therapeutic agent is conjugated to the peptide moiety through an amino group via a peptide bond linkage and the metal is chelated to the glycoside. 
     
     
         4 . The glycopeptide of  claim 1 , wherein the glycoside moiety comprises at least two covalently bound monomeric units and wherein the peptide moiety comprises a poly(amino acid). 
     
     
         5 . The glycopeptide of  claim 1 , wherein the glycoside moiety comprises an aminated sugar. 
     
     
         6 . The glycopeptide of  claim 1 , wherein the glycoside moiety comprises chitosan and the peptide moiety comprises poly(glutamic acid) or poly(aspartic acid). 
     
     
         7 . The glycopeptide of  claim 1 , wherein the glycopeptide comprises the peptide moiety in an amount of from about 5% to about 50% by weight of the glycopeptide. 
     
     
         8 . The glycopeptide of  claim 1 , wherein the glycoside moiety has a molecular weight of from about 3,000 daltons to about 10,000 daltons, and wherein the peptide moiety has a molecular weight of from about 750 daltons to about 3,000. 
     
     
         9 . The glycopeptide of  claim 1 , wherein the glycopeptide has a molecular weight of from about 5,000 daltons to about 30,000 daltons. 
     
     
         10 . The glycopeptide of  claim 1 , wherein the glycoside is selected from the group consisting of: collagen, chondroitin, hyauraniate, and heparin, and any combinations thereof, and wherein the peptide is selected from the group consisting of: poly(glutamic acid) and poly(aspartic acid), and any combinations thereof. 
     
     
         11 . The glycopeptide of  claim 1 , wherein the diagnostic or therapeutic agent is selected from the group consisting of: anticancer drugs, rheumatoid arthritis drugs, anticoagulants, anti-angiogenesis drugs, apoptosis drugs, osteoporosis drugs, steroids, anti-inflammatory drugs, and any combinations thereof. 
     
     
         12 . The glycopeptide of  claim 1 , wherein the diagnostic or therapeutic agent comprises methotrexate or pamidronate. 
     
     
         13 . The glycopeptide of  claim 2 , wherein the metal comprises a radionuclide. 
     
     
         14 . The glycopeptide of  claim 13 , wherein the metal is selected from the group consisting of: Tc-99m, Cu-60, Cu-61, Cu-62, Cu-67, In-111, T1-201, 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. 
     
     
         15 . The glycopeptide of  claim 1 , wherein the glycopeptide comprises the diagnostic or therapeutic agent in an amount of from about 10% to about 60% by weight of the glycopeptide. 
     
     
         16 . The glycopeptide of  claim 1 , wherein the glycoside targets vascular endothelial cells and the peptide targets cancer cells. 
     
     
         17 . A glycopeptide comprising: chitosan; and a poly(amino acid), wherein the chitosan and poly(amino acid) are covalently bound through an amide bond. 
     
     
         18 . The glycopeptide of  claim 17 , wherein the chitosan comprises alkyl sulfonated chitosan. 
     
     
         19 . The glycopeptide of  claim 17 , wherein the poly(amino acid) comprises poly(glutamic acid) or poly(aspartic acid). 
     
     
         20 . The glycopeptide of  claim 17 , further comprising a diagnostic or therapeutic agent conjugated to the poly(amino acid). 
     
     
         21 . The glycopeptide of  claim 17 , further comprising a metal conjugated to the chitosan. 
     
     
         22 . A method of producing a glycopeptide comprising 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 peptide. 
     
     
         23 . The method of  claim 22 , further comprising forming an amide or ester bond between the peptide and a diagnostic or therapeutic agent. 
     
     
         24 . The method of  claim 22 , further comprising conjugating a chelating agent and a metal to the glycoside.