Derivative Peptide Compounds and Methods of Use

Abstract

The present invention provides synthetic peptide compounds and uses thereof for therapy and diagnostics of complement-mediated diseases, such as inflammatory diseases, autoimmune diseases, and microbial and bacterial infections and non-complement-mediated diseases, such cystic fibrosis and various acute diseases. The invention is directed to modifications of a synthetic peptide of 15 amino acids from the Polar Assortant (PA) peptide, which is a scrambled peptide derived from human Astrovirus protein. In some embodiments, the invention is directed to peptide compounds that are peptide mimetics, peptide analogs and/or synthetic derivatives of PA (e.g., sarcosine derivatives) having, for example, internal peptide substitutions, and modifications, including PEGylation at the N-terminus and C-terminus. The invention further provides methods of selecting at least one synthetic peptide for treating various conditions.

What is claimed is: 
     
         1 . A synthetic peptide comprising at least about 90% sequence identity to an amino acid sequence of SEQ ID NO: 3-47. 
     
     
         2 . The synthetic peptide of  claim 1  comprising the amino acid sequence and modifications of SEQ NO: 4-18 and 30-47. 
     
     
         3 . The synthetic peptide of  claim 1  comprising the amino acid sequence and modifications of SEQ ID NO: 3 and 19-29. 
     
     
         4 . The synthetic peptide of  claim 3  comprising the amino acid sequence and PEGylation modifications of SEQ ID NO: 21. 
     
     
         5 . A pharmaceutical composition comprising a therapeutically effective amount of the synthetic peptide of  claim 1  and at least one pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
         6 . A method of treating and/or preventing a hemolytic reaction in a subject in need thereof comprising: administering to the subject in need thereof a composition comprising a therapeutically effective amount of a synthetic peptide comprising at least about 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 3-47. 
     
     
         7 . The method of  claim 6 , wherein the method of treating and/or preventing a hemolytic reaction in a subject in need thereof comprises: administering to the subject having a hemolytic reaction a composition comprising a therapeutically effective amount of a synthetic peptide selected from the group consisting of SEQ ID NO: 3-47. 
     
     
         8 . The method of  claim 6 , wherein the hemolytic reaction is selected from the group consisting of acute intravascular hemolytic transfusion reaction (AIHTR), transfusion related acute lung injury (TRALI), and platelet transfusion refractoriness. 
     
     
         9 . The method of  claim 6 , wherein the composition is administered before the subject is administered a blood transfusion, after the subject is administered the blood transfusion, and/or during the blood transfusion. 
     
     
         10 . The method of  claim 6 , wherein the composition comprises at least one pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
         11 . A method of treating hypoxic ischemic encephalopathy in a subject in need thereof comprising: administering to the subject in need thereof, a composition comprising a therapeutically effective amount of a synthetic peptide comprising at least about 90% sequence identity to at least one amino acid sequence selected from the group consisting of SEQ ID NO: 3-47. 
     
     
         12 . The method of  claim 11 , wherein the method of treating hypoxic ischemic encephalopathy in a subject in need thereof comprises administering to the subject in need thereof a composition comprising a therapeutically effective amount of at least one synthetic peptide selected from the group consisting of SEQ ID NO: 3-47. 
     
     
         13 . The method of  claim 11 , wherein the composition comprises at least one pharmaceutically acceptable carrier, diluent, or excipient.