High-affinity antagonists of ELR-CXC chemokines

Abstract

The present invention provides novel polypeptide sequences, methods for production thereof and uses thereof for novel ELR—CXC chemokine receptor agonists and antagonists.

1 . An isolated or purified peptide comprising an amino acid sequence of: X 1 ELRCXCIRX XSXPFXPKXI XEXXXIXSPP HCXNXEIIVK LXXGXEXCLX PXXXWVQXXV XXFXKXXEXX 2 X 3 X 4    
       wherein X 1 , X 2 , X 3  and X 4  are independently 0-10 amino acid residues.  
     
     
         2 . The peptide according to  claim 1  wherein X 1  is 0-8 amino acids.  
     
     
         3 . The peptide according to  claim 1  wherein each X 1  is 0-6 amino acids.  
     
     
         4 . The peptide according to  claim 1  wherein X 1  is selected from the group consisting of GSK, GST, S, A, T, K, GSMGGSK, and GSMGGST.  
     
     
         5 . The peptide according to  claim 1  wherein X 1  is deleted.  
     
     
         6 . An isolated or purified peptide comprising an amino acid sequence of: X 1 ELRCX 6 CIRX 10 X 11 SX 13 PFX 16 PKX 19 I X 21 EX 23 X 24 X 25 1X 27 SPP HCX 33 NX 35 EIIVK LX 42 X 43 GX 45 EX 47 CLX 50  PX 52 X 53 X 54 WVQX 58 X 59 V X 61 X 62 FX 64 KX 66 X 67 EX 69 X 70 X 71 X 72  (defined consensus SEQ ID No. 4)  
       wherein 
 X 1  is 0-10 amino acids;  
 X 6  is Q, E or L;  
 X 10  is T or i;  
 X 11  is H or Y;  
 X 13  is T or K;  
 X 16  is H or N;  
 X 19  is F or Y or L;  
 X 21  is K or R;  
 X 23  is L or M;  
 X 24  is R or T;  
 X 25  is V or A;  
 X 27  is D or E;  
 X 33  is V or A or E;  
 X 35  is T or S;  
 X 42  is S or V or T or F;  
 X 43  is D or N;  
 X 45  is R or A or N or K or D;  
 X 47  is L or V;  
 X 50  is D or N;  
 X 52  is K or H;  
 X 53  is E or Q or T;  
 X 54  is P or N or K;  
 X 58  is R or K or I;  
 X 59  is V or I;  
 X 61  is E or Q;  
 X 62  is K or I or V or A;  
 X 64  is L or V;  
 X 66  is R or K;  
 X 67  is A or T;  
 X 69  is S or N or K or G;  
 X 70  is Q or S or K or deleted;  
 X 71  is N or D or deleted; and  
 X 72  is P or A or S or deleted.  
 
     
     
         7 . The peptide according to  claim 6  wherein X 1  is 0-8 amino acids.  
     
     
         8 . The peptide according to  claim 6  wherein Xis 0-6 amino acids.  
     
     
         9 . The peptide according to  claim 6  wherein X 1  is S, A, T, K, GSK, GST, GSMGGSK, GSMGGST or deleted.  
     
     
         10 . An isolated peptide consisting essentially of an amino acid sequence as set forth in any one of SEQ ID No. 10-41.