Synthetic peptides having FGF receptor affinity

Abstract

Peptidic compositions having FGF receptor affinity, as well as fusion proteins and oligomers of the same, are provided. The subject peptidic compounds are characterized by having little or no homology to naturally occurring bFGF. The subject fusion proteins include the peptidic composition linked to an oligomerization domain, either directly or through a linking group and optionally further include a heparin binding domain. The subject peptidic compositions, fusion proteins and oligomers thereof find use in a variety of applications, including both research and therapeutic applications, in which FGF receptor ligands are employed.

What is claimed is:  
     
         1 . A peptidic compound capable of binding to an FGF receptor, wherein the sequence of said peptidic compound has, at most, low sequence identity to a naturally occurring FGF.  
     
     
         2 . The peptidic compound according to  claim 1 , wherein said peptidic compound is an FGF receptor antagonist.  
     
     
         3 . The peptidic compound according to  claim 1 , wherein said peptidic compound is an FGF receptor agonist.  
     
     
         4 . The peptidic compound according to  claim 3 , wherein said peptidic compound exhibits at least one bFGF activity selected from the group consisting of: (a) displacement of bFGF from an FGF receptor; (2) stimulation of MAP kinase phosphorylation in FGF receptor expressing 293 cells; (3) stimulation of FGF receptor autophosphorylation; and (4) stimulation of BrdU incorporation in Swiss 3T3 cells.  
     
     
         5 . The peptidic compound according to  claim 1 , wherein said peptidic compound is a peptide.  
     
     
         6 . The peptidic compound according to  claim 1 , wherein said peptidic compound comprises from about 10 to 30 monomeric units.  
     
     
         7 . The peptidic compound according to  claim 1 , wherein said peptidic compound comprises a sequence selected from the group consisting of SEQ ID NOS: 1-39.  
     
     
         8 . A peptide having a sequence that is identical to or substantially the same as AESGDDYCVLVFTDSAWTKICDWSHFRN (SEQ ID NO:38).  
     
     
         9 . A fusion protein comprising: 
 (a) a variable domain comprising a peptidic compound according to  claim 1;  and    (b) an oligomerization domain.    
     
     
         10 . The fusion protein according to  claim 9 , wherein said variable domain comprises a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-39.  
     
     
         11 . The fusion protein according to  claim 9 , wherein said fusion protein further comprises a heparin binding domain.  
     
     
         12 . The fusion protein according to  claim 9 , wherein said oligomerization domain is a homodimerization domain.  
     
     
         13 . A fusion protein having the sequence identical to or substantially the same as the sequence of SEQ ID NO:41 or SEQ ID NO:43.  
     
     
         14 . An oligomer of a peptidic compound according to  claim 1 .  
     
     
         15 . The oligomer according to  claim 14 , wherein said oligomer is a homodimer.  
     
     
         16 . The homodimer according to  claim 15 , wherein said homodimer is a dimer of a fusion protein according to  claim 9 .  
     
     
         17 . A polynucieotide encoding a peptidic compound according to  claim 1 , a peptide according to  claim 8 , or a fusion protein according to  claim 13 .  
     
     
         18 . An expression system comprising a polynucleotide according to  claim 17 .  
     
     
         19 . The expression system according to  claim 18 , wherein said expression system is present in a vector.  
     
     
         20 . A host cell comprising the expression system according to  claim 18 .  
     
     
         21 . A pharmaceutical composition comprising one of: (a) a peptidic compound according to  claim 1;  (b) a fusion protein according to  claim 9;  or (c) an oligomer according to  claim 14 .  
     
     
         22 . A method for producing bFGF activity in a host, said method comprising: 
 administering to said host an effective amount of a pharmaceutical composition according to  claim 21 .    
     
     
         23 . A method of treating a subject for a condition treatable with bFGF activity, said method comprising: 
 administering to said host an effective amount of the pharmaceutical composition according to  claim 21 .    
     
     
         24 . A method of targeting an agent to an FGF receptor in a host, said method comprising: 
 administering to said host an effective amount of a pharmaceutical composition according to  claim 21 , wherein said peptidic compound, fusion protein or oligomer is conjugated to said agent.