Integrin binding motif containing peptides and methods of treating skeletal diseases

Abstract

Peptide sequences comprising 10 to 50 amino acids are disclosed. The sequences are characterized by containing at least one of an integrin binding motif such as an RGD sequence, a glycosaminoglycan binding motif, and a calcium binding motif, and the remainder of amino acids contiguous with the RGD sequence in matrix extracellular phosphoglycoprotein. The sequences may be formulated for injection or dispersed in toothpaste or a mouthwash or gum patch and administered to enhance bone/tooth growth and/or reduce excessive urinary phosphate loss from the body.

1 .- 13 . (canceled) 
     
     
         14 . A method of reducing bone loss, comprising:
 administering to an individual a therapeutically effective amount of a formulation comprising:   a carrier; and   a peptide compound comprising at least 10 and not more than 50 naturally occurring amino acids the peptide compound comprising an RGD integrin binding motif, an SGDG glycosaminoglycan binding motif, and a calcium binding motif.   
     
     
         15 . The method of  claim 14 , wherein the calcium binding motif has the sequence DXDXSXFXGXXQ, wherein X is any amino acid. 
     
     
         16 . The method of  claim 15 , wherein the calcium binding motif has the sequence DNDISPFSGDGQ. 
     
     
         17 . The method of  claim 14 , wherein the carrier is a saline solution and the formulation is injectable. 
     
     
         18 . The method of  claim 14 , wherein the peptide comprises an amino acid sequence contiguous with a RGD sequence of naturally occurring matrix extracellular phosphoglycoprotein. 
     
     
         19 . The method of  claim 14 , wherein the formulation comprises 1 μg to 1,000 μg of peptide. 
     
     
         20 . The method of  claim 14 , wherein the formulation comprises 10,000 μg to 50,000 μg of peptide. 
     
     
         21 . The method of  claim 14 , wherein the formulation comprises 10,000 μg to 25,000 μg of peptide. 
     
     
         22 . The method as claimed in  claim 14 , further comprising:
 administering an additional active ingredient consisting of estrogen, calcitonin, vitamin D, fluoride, Ipriflavon and a bisphosphonate   
     
     
         23 . The method of  claim 14 , wherein the peptide compound is a multimer. 
     
     
         24 . A patch for transdermal delivery of a peptide, a patch comprising:
 a carrier; and   a peptide compound comprising at least 10 and not more than 50 naturally occurring amino acids the peptide compound comprising an integrin binding motif, a glycosaminoglycan binding motif, and a calcium binding motif.   
     
     
         25 . A method of reducing renal phosphate excretion in an individual, comprising:
 administering to an individual a therapeutically effective amount of a formulation comprising:   a carrier; and   a peptide compound comprising at least 10 and not more than 50 naturally occurring amino acids the peptide compound comprising an RGD integrin binding motif, an SGDG glycosaminoglycan binding motif, and a calcium binding motif.   
     
     
         26 . The method of  claim 25 , wherein the calcium binding motif has the sequence DXDXSXFXGXXQ, wherein X is any amino acid. 
     
     
         27 . The method of  claim 25 , wherein the calcium binding motif has the sequence DNDISPFSGDGQ. 
     
     
         28 . The method of  claim 25 , wherein the carrier is a saline solution and the formulation is injectable.