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 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 integrin binding motif, a glycosaminoglycan binding motif, and a calcium binding motif.    
     
     
         15 . The peptide compound of  claim 14 , wherein the integrin binding motif is an RGD sequence.  
     
     
         16 . The peptide compound of  claim 14 , wherein the glycosaminoglycan motif has the sequence SGDG.  
     
     
         17 . The peptide compound of  claim 14 , wherein the calcium binding motif has the sequence DXDXSXFXGXXQ, wherein X is any amino acid.  
     
     
         18 . The peptide compound of  claim 17 , wherein the calcium binding motif has the sequence DNDISPFSGDGQ.  
     
     
         19 . A multimer of the peptide of  claim 14 .  
     
     
         20 . The formulation according to  claim 14 , wherein the carrier is a saline solution and the formulation is injectable.  
     
     
         21 . The formulation according to  claim 14 , wherein the carrier is a paste and the formulation is a toothpaste.  
     
     
         22 . The formulation according to  claim 14 , wherein the carrier is an aqueous flavored solution and the formulation is a mouthwash.  
     
     
         23 . A patch for oral delivery of a compound, said patch comprising a formulation according to  claim 14   
     
     
         24 . A method of reducing bone loss, comprising administering to an individual an effective amount of a peptidic compound according to  claim 14 .  
     
     
         25 . A method of reducing renal phosphate excretion in an individual, comprising administering to an individual an effective amount of a peptidic compound according to  claim 14 .  
     
     
         26 . The formulation of  claim 14 , wherein the peptide comprises an amino acid sequence contiguous with a RGD sequence of naturally occurring matrix extracellular phosphoglycoprotein.