Fibroblast Growth Factor Receptor-Derived Peptides Binding to NCAM

Abstract

The present invention relates to the use of peptides that are capable of binding to, and modulating the activity of NCAM. The peptides are peptide fragments of FGFRs. They are derived from two distinct binding sites for binding of the immunoglobulin-like module 2 of FGFR to NCAM F3 modules 1-2. The invention further relates to use of said peptides for the production of a medicament for the treatment of different pathological conditions, wherein NCAM and/or FGFRs play a prominent role.

1 .- 35 . (canceled) 
     
     
         36 . A method for modulating NCAM signaling comprising administering to a subject in need thereof an isolated peptide of 5 to 25 contiguous amino acids, said peptide comprising an amino acid sequence derived from FGFR Ig2 and selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   TSPEKMEKKL 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   AKTVKFK 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   RWLKNGKEFK 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   TWSIIMDSV 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   SDKGNYTCIVEN 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   TYQLDVVERS, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or a fragment or variant thereof, said variant being at least 70% identical to said amino acid sequence, and said fragment having a length of 5 or more amino acid residues, wherein said peptide specifically binds to NCAM. 
     
     
         37 . The method according to  claim 36 , wherein said peptide is in monomeric form. 
     
     
         38 . The method according to  claim 36 , wherein said peptide is in multimeric form. 
     
     
         39 . The method according to  claim 36 , wherein said variant is at least 80% identical to said amino acid sequence. 
     
     
         40 . The method according to  claim 36 , wherein said peptide is 5 to 15 amino acids in length. 
     
     
         41 . The method according to  claim 36 , wherein said peptide specifically binds to the NCAM fibronectin 3, module 1 or 2. 
     
     
         42 . The method according to  claim 36 , wherein said peptide activates NCAM signaling. 
     
     
         43 . The method according to  claim 36 , wherein said peptide induces neurite outgrowth and/or promotes neural cell survival and/or stimulates synaptic plasticity and/or stimulates learning and/or memory including short term and long term memory. 
     
     
         44 . The method according to  claim 36 , wherein said peptide comprises the amino acid sequence of SEQ ID NO:2, or a fragment having at least 5 consecutive amino acids of SEQ ID NO:2. 
     
     
         45 . The method according to  claim 36 , wherein said peptide comprises the amino acid sequence of SEQ ID NO:3, or a fragment having at least 5 consecutive amino acids of SEQ ID NO:3. 
     
     
         46 . The method according to  claim 36 , wherein said peptide comprises or consists of the amino acid sequence of SEQ ID NO:2, or a variant having at least 80% identity to SEQ ID NO:2. 
     
     
         47 . The method according to  claim 36 , wherein said peptide comprises or consists of the amino acid sequence of SEQ ID NO:3, or a variant having at least 70% identity to SEQ ID NO:3. 
     
     
         48 . The method according to  claim 36 , wherein said peptide comprises or consists of the amino acid sequence of SEQ ID NO:3, or a variant having at least 80% identity to SEQ ID NO:3. 
     
     
         49 . The method according to  claim 36  wherein the subject has a disease or condition of the central nervous system or the peripheral nervous system. 
     
     
         50 . The method according to  claim 36  wherein the subject has a condition selected from the group consisting of postoperative nerve damage, traumatic nerve damage, impaired myelination of nerve fibers, post-ischaemic damage, multi-infarct dementia, multiple sclerosis, nerve degeneration associated with diabetes mellitus, neuromuscular degeneration, schizophrenia, mood disorders, manic depressive disorders, prion diseases, cancer, Alzheimer's disease, Parkinson's disease, and Huntington's disease. 
     
     
         51 . The method according to  claim 36  wherein the subject has a disease or condition of the muscles, or a disease or degenerative condition of the gonads, of the pancreas, of the kidney or of the heart. 
     
     
         52 . The method according to  claim 36  wherein the subject has acute myocardial infarction. 
     
     
         53 . The method according to  claim 36  wherein the subject has a wound and wherein the peptide promotes wound healing. 
     
     
         54 . A pharmaceutical composition comprising an isolated peptide as defined in  claim 36 . 
     
     
         55 . A method for modulating NCAM signaling comprising administering to a subject in need thereof an isolated peptide consisting of an amino acid sequence derived from FGFR Ig2 and selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   TSPEKMEKKL 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   AKTVKFK 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   RWLKNGKEFK 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   TWSIIMDSV 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   SDKGNYTCIVEN 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   TYQLDVVERS 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or a fragment or variant thereof, said variant being at least 70% identical to said amino acid sequence, and said fragment having a length of 5 or more amino acid residues, wherein said peptide specifically binds to NCAM.