IGF antagonist peptides

Abstract

Peptides are provided that antagonize the interaction of IGF-1 with its binding proteins, insulin receptor, and IGF receptor. These IGF antagonist peptides are useful in treating disorders involving IGF-1 as a causative agent, such as, for example, various cancers.

1 . A peptide comprising the sequence: 
 (Xaa) 1 (Xaa) 2 Cys(Xaa) 3 (Xaa) 4 Asp(Xaa) 5 (Xaa) 6 Gly(Xaa) 7 (Xaa) 8 TyrCysTrp(Xaa) 9  (SEQ ID NO:5), where (Xaa) 1 , (Xaa) 4 , and (Xaa) 8  are an amino acid, (Xaa) 2  is Arg, Lys, Gly, Ser, or Thr, (Xaa) 3  is Ala or Val, (Xaa) 5  is Ala or Leu, (Xaa) 6  is Ala, Gly, or Leu, (Xaa) 7  is Phe, Tyr, Trp, or Gly, and (Xaa) 9  is Glu, Asp, Ala, or Gly.    
   
   
       2 . The peptide of  claim 1  wherein the amino acids in the peptide are all L-amino acids.  
   
   
       3 . The peptide of  claim 1  further comprising a glycine residue after (Xaa) 9 .  
   
   
       4 . The peptide of  claim 1  wherein (Xaa) 2  is Gly, Ser, Arg, or Thr, and (Xaa) 9  is Glu, Ala, or Asp.  
   
   
       5 . The peptide of  claim 1  wherein (Xaa) 2  is Glu or Arg, (Xaa) 5  is Leu, (Xaa) 6  is Ala or Gly, (Xaa) 7  is Phe, and (Xaa) 9  is Ala.  
   
   
       6 . The peptide of  claim 1  that comprises the sequence LGCASDLAGFWYCWAG (SEQ ID NO:6) or WRCVDDLGGFQYCWAG (SEQ ID NO:7).  
   
   
       7 . The peptide of  claim 1  that is conjugated to a cytotoxic agent or polyethylene glycol.