Peptide inhibitors of calcium oxalate monohydrate crystallization and uses thereof

Abstract

In an embodiment, the present disclosure pertains to a composition for inhibiting calcium oxalate monohydrate crystal growth comprising at least one isolated polypeptide comprising a plurality of amino acids that bind the surface of the calcium oxalate monohydrate crystal; and a plurality of amino acids spacers, wherein the amino acid spacers are arranged in varying sequences between the plurality of amino acids that bind the surface of the calcium oxalate monohydrate crystal. In some embodiments, the present disclosure related to a method of controlling calcium oxalate monohydrate crystal growth in a subject in need thereof comprising administering to the subject therapeutically effective amount of the calcium oxalate monohydrate inhibiting polypeptide. In some embodiments, the present disclosure relates to a method of identifying calcium oxalate monohydrate inhibiting peptides.

What is claimed is: 
     
         1 . A method comprising:
 administering to a subject a composition comprising:
 at least one isolated polypeptide; and 
 at least one pharmaceutically acceptable carrier, 
 wherein the at least one isolated polypeptide comprises one or more amino acids that act as a binder to bind to a surface of a calcium oxalate monohydrate crystal, and 
 wherein the one or more amino acids that act as the binder comprise at least one of glutamic acid (E), aspartic acid (D), and combinations thereof. 
   
     
     
         2 . The method of  claim 1 , wherein the administering inhibits abnormal biomineralization in the subject. 
     
     
         3 . The method of  claim 1 , wherein the at least one isolated polypeptide inhibits calcium oxalate monohydrate crystal growth in the subject. 
     
     
         4 . The method of  claim 1 , wherein the method is utilized to treat or prevent a disease in the subject. 
     
     
         5 . The method of  claim 4 , wherein the disease is associated with abnormal biomineralization. 
     
     
         6 . The method of  claim 4 , wherein the disease is selected from the group consisting of recurrent kidney stone disease, recurrent stone disease, calcium oxalate stone disease, primary hyperoxaluria, systemic oxalosis, renal calcification disorder, and combinations thereof. 
     
     
         7 . The method of  claim 1 , further comprising using ultrasound therapy. 
     
     
         8 . The method of  claim 1 , wherein the at least one isolated polypeptide further comprises one or more amino acids that act as a spacer to minimize the steric hindrance of the amino acid binder to the surface of the calcium oxalate monohydrate crystal. 
     
     
         9 . The method of  claim 8 , wherein the one or more amino acids that act as the spacer comprise alanine (A). 
     
     
         10 . The method of  claim 1 , wherein the at least one isolated polypeptide comprises an amino acid sequence selected from the group consisting of DDDAAAAADDDAAAAADD (SEQ ID NO: 1), AADAAAAADDAAAADAAA (SEQ ID NO: 2), ADAAADAADAADDAADAA (SEQ ID NO: 3), ADAADAADAADAADAADA (SEQ ID NO: 4), ADAADDAADAADDAAAAA (SEQ ID NO: 5), ADAAADDDAAADAAADDD (SEQ ID NO: 6), ADAAADDAAAAAAAADAA (SEQ ID NO: 7), ADAAADDAAADAAAADAA (SEQ ID NO: 8), ADAAADDAAADAAADDAA (SEQ ID NO: 9), ADAADAAADAADDAADAA (SEQ ID NO: 10), ADAADDAAAAAADAADAA (SEQ ID NO: 11), ADDAADAADAADDAADDA (SEQ ID NO: 12), ADADADADADADADADAD (SEQ ID NO: 13), AAEAAAAAEEAAAAEAAA (SEQ ID NO: 14), AEAAAEAAEAAEEAAEAA (SEQ ID NO: 15), AEAAEAAEAAEAAEAAEA (SEQ ID NO: 16), AEAAAEEAAAEAAAAEAA (SEQ ID NO: 17), AEAAAEEAAAEAAAEEAA (SEQ ID NO: 18), AEAAEAAAEAAEEAAEAA (SEQ ID NO: 19), AEAAEEAAAAAAEAAEAA (SEQ ID NO: 20), AEEAAEAAEAAEEAAEEA (SEQ ID NO: 21), AEEAEEAEEAEEAEEAEE (SEQ ID NO: 22), AEAEAEAEAEAEAEAEAE (SEQ ID NO: 23), EEEEEEEEEEEEEEEEEE (SEQ ID NO: 24), and combinations thereof. 
     
     
         11 . The method of  claim 1 , wherein the isolated polypeptide comprises an amino acid sequence selected from the group consisting of DDDAAAAADDDAAAAADD (SEQ ID NO: 1), AADAAAAADDAAAADAAA (SEQ ID NO: 2), ADAAADAADAADDAADAA (SEQ ID NO: 3), ADAADDAADAADDAAAAA (SEQ ID NO: 5), ADAAADDDAAADAAADDD (SEQ ID NO: 6), ADAAADDAAAAAAAADAA (SEQ ID NO: 7), ADAAADDAAADAAAADAA (SEQ ID NO: 8), ADAAADDAAADAAADDAA (SEQ ID NO: 9), ADAADAAADAADDAADAA (SEQ ID NO: 10), ADAADDAAAAAADAADAA (SEQ ID NO: 11), ADDAADAADAADDAADDA (SEQ ID NO: 12), AAEAAAAAEEAAAAEAAA (SEQ ID NO: 14), AEAAAEAAEAAEEAAEAA (SEQ ID NO: 15), AEAAAEEAAAEAAAAEAA (SEQ ID NO: 17), AEAAAEEAAAEAAAEEAA (SEQ ID NO: 18), AEAAEAAAEAAEEAAEAA (SEQ ID NO: 19), AEAAEEAAAAAAEAAEAA (SEQ ID NO: 20), AEEAAEAAEAAEEAAEEA (SEQ ID NO: 21), AEEAEEAEEAEEAEEAEE (SEQ ID NO: 22), and combinations thereof. 
     
     
         12 . The method of  claim 1 , wherein the isolated polypeptide comprises an amino acid sequence selected from the group consisting of ADAADAADAADAADAADA (SEQ ID NO: 4), ADADADADADADADADAD (SEQ ID NO: 13), AEAAEAAEAAEAAEAAEA (SEQ ID NO: 16), AEAEAEAEAEAEAEAEAE (SEQ ID NO: 23), EEEEEEEEEEEEEEEEEE (SEQ ID NO: 24), and combinations thereof.