Heparin binding motif and use thereof

Abstract

A method for reducing cytotoxicity of eosinophil derived toxins comprising administering to a subject an effective amount of heparin, heparan sulfate, a potent heparanase inhibitor or a polypeptide which has sequence as follows: BZBXBX, XBBBXXBX, XBBXBX, BBXXBBBXXBB, BXBBXB, XBBBXXBBBXXBBX, or TXXBXXTBXXXTBB, wherein X represents any amino acid, Z represents an aromatic amino acid, and B represents a basic amino acid and T represents a turn.

1 . A heparin binding motif comprising BZBXBX, wherein X represents any amino acid, Z represents an aromatic amino acid and B represents a basic amino acid, provided that the motif excludes SEQ ID NO. 8. 
     
     
         2 . The heparin binding motif of  claim 1 , which is derived from eosinophil cationic protein comprises the sequence of  claim 1 . 
     
     
         3 . A method for reducing cytotoxicity of eosinophil derived toxins comprising administering to a subject an effective amount of heparin, heparan sulfate, potent heparanase inhibitor or a polypeptide which has sequence as follows: BZBXBX, XBBBXXBX, XBBXBX, BBXXBBBXXBB, BXBBXB, XBBBXXBBBXXBBX, or TXXBXXTBXXXTBB, wherein X represents any amino acid, Z represents an aromatic amino acid, B represents a basic amino acid and T represents a turn. 
     
     
         4 . The method of  claim 3 , wherein the polypeptide comprising a high portion of positively charged residues. 
     
     
         5 . The method of  claim 3 , wherein the polypeptide comprises QRRCKN (SEQ ID NO:7) or RWRCKN (SEQ ID NO:8). 
     
     
         6 . The method of  claim 3 , wherein the polypeptide is SEQ ID NO: 3 (NYRWRCKNQNK) or SEQ ID NO: 4 (NYQRRCKNQNK). 
     
     
         7 . The method of  claim 3 , wherein the heparin comprises low molecular weight heparin (LMWH), high molecular weight heparin (HMWH), heparan sulfate proteoglycans (HSPG) or synthetic heparin oligosaccharides and heparan sulfates. 
     
     
         8 . The method of  claim 7 , wherein the synthetic heparin oligosaccharides comprises degree of polymerization (dp) 3 to 15. 
     
     
         9 . The method of  claim 7 , wherein the synthetic heparan sulfates comprises degree of polymerization (dp) 5 to 9. 
     
     
         10 . The method of  claim 3 , wherein the cytotoxicity of eosinophil derived toxins is reduced by reducing endocytosis of eosinophil derived toxins. 
     
     
         11 . The method of  claim 10 , wherein the eosinophil derived toxins is eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO, also called EPX), or major basic protein (MBP). 
     
     
         12 . The method of  claim 3 , wherein the subject is mammalian. 
     
     
         13 . The method of  claim 3 , which further inhibits asthma. 
     
     
         14 . The method of  claim 13 , wherein the asthma is ECP/EDN-induced asthma, cytotoxic RNase-induced asthma or high pI toxin-induced asthma.