Method and peptide for regulating cellular activity

Abstract

Method and peptide for regulating cellular activity includes a panel of synthesized peptides that have biological effects on inhibiting or enhancing cellular activity. Selected peptides can be used as therapy to reduce and/or inhibit, or initiate and/or enhance, an inflammatory response in a subject.

What is claimed is: 
     
         1 . An isolated polypeptide, consisting of:
 (a) the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15; or   (b) the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15, covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22.   
     
     
         2 . The isolated polypeptide of  claim 1 , optionally modified with a fluorescent label. 
     
     
         3 . The isolated polypeptide of  claim 1 , consisting of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15. 
     
     
         4 . The isolated polypeptide of  claim 1 , consisting of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15, covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22. 
     
     
         5 . A pharmaceutical composition comprising an effective amount of the polypeptide of  claim 1  and a carrier. 
     
     
         6 . A method of inhibiting Toll Like Receptor (TLR)-induced cytokine secretion to a subject in need thereof, comprising:
 administering to the subject in need thereof, an effective amount of the isolated polypeptide of  claim 1 ,   thereby inhibiting the Toll Like Receptor (TLR)-induced cytokine secretion.   
     
     
         7 . The method of  claim 6 , comprising administering to the subject an effective amount of a peptide consisting of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15, covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22; thereby inhibiting Toll Like Receptor (TLR)-induced cytokine secretion. 
     
     
         8 . The method of  claim 6 , wherein the peptide consists of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15. 
     
     
         9 . A method of reducing or inhibiting Toll Like Receptor (TLR)-induced inflammation, comprising: administering to a subject in need thereof, an effective amount of:
 a) a peptide consisting of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO; 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15; or   b) a peptide consisting of the amino acid sequence set forth as SEQ ID NO: 1, the amino acid sequence set forth as SEQ ID NO: 10, the amino acid sequence set forth as SEQ ID NO: 4, the amino acid sequence set forth as SEQ ID NO: 2, the amino acid sequence set forth as SEQ ID NO: 3, the amino acid sequence set forth as SEQ ID NO: 5, the amino acid sequence set forth as SEQ ID NO: 9, the amino acid sequence set forth as SEQ ID NO: 11, the amino acid sequence set forth as SEQ ID NO: 12, or the amino acid sequence set forth as SEQ ID NO: 15, covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22;   thereby reducing or inhibiting Toll Like Receptor (TLR)-induced inflammation.   
     
     
         10 . The method of  claim 9 , wherein the inflammation is caused by a bacteria. 
     
     
         11 . The method of  claim 9 , wherein the bacteria is  Streptococcus pneumoniae.    
     
     
         12 . The method of  claim 9 , wherein the subject has otitis media. 
     
     
         13 . The method of  claim 9 , wherein the TLR is one or more of TLR 2, TLR3, TLR4, TLR5 and TLR9. 
     
     
         14 . The method of  claim 13 , wherein the TLR is TLR2. 
     
     
         15 . The method of  claim 13 , wherein the TLR is TLR3. 
     
     
         16 . The method of  claim 13 , wherein the TLR is TLR4. 
     
     
         17 . The method of  claim 13 , wherein the TLR is TLR5. 
     
     
         18 . The method of  claim 13 , wherein the TLR is TLR9. 
     
     
         19 . The method of  claim 6 , wherein the TLR is one or more of TLR2, TLR3, TLR4, TLR5 and TLR9. 
     
     
         20 . The isolated polypeptide of  claim 1 , consisting of:
 (a) the amino acid sequence set forth as SEQ ID NO: 1; or   (b) the amino acid sequence set forth as SEQ ID NO: 1 covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22.   
     
     
         21 . The isolated polypeptide of  claim 1 , consisting of:
 (a) the amino acid sequence set forth as SEQ ID NO: 10; or   (b) the amino acid sequence set forth as SEQ ID NO: 10 covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22.   
     
     
         22 . The isolated polypeptide of  claim 1 , consisting of:
 (a) the amino acid sequence set forth as SEQ ID NO: 4; or   (b) the amino acid sequence set forth as SEQ ID NO: 4 covalently linked to the transducing amino acid sequence set forth as SEQ ID NO: 22.