Compounds and methods of modulating angiogenesis

Abstract

A pharmaceutical composition includes a synthetic peptide consisting of about 10 to about 50 amino acids and having an amino acid sequence substantially homologous to consecutive amino acids of a portion of the cytoplasmic doman of at least one of α v β 3 integrin or VEGFR2 that includes a tyrosine residue, the amino acid sequence of the peptide including a phosphorylated tyrosine residue or a γ-carboxyglutamic acid residue that is substituted for a corresponding tyrosine residue of the portion of the cytoplasmic domain of α v β 3 integrin or VEGFR2.

1 - 15 . (canceled) 
     
     
         16 : A pharmaceutical composition comprising: a synthetic peptide, the peptide comprises an amino acid sequence substantially homologous to about 5 to about 30 consecutive amino acids of a portion of the cytoplasmic domain of α v β 3  integrin that includes a tyrosine residue, the amino acid of the peptide including an amino acid that structurally mimics a phosphorylated tyrosine reside that substitutes a corresponding tyrosine residue of the portion of the cytoplasmic domain of α v β 3  integrin, the peptide is about 10 to about 50 amino acids in length, and the peptide inhibits interaction of α v β 3  integrin with VEGFR2. 
     
     
         17 : The pharmaceutical composition of  claim 16 , the peptide not inhibiting natural ligand binding to the α v β 3  integrin. 
     
     
         18 : The pharmaceutical composition of  claim 16 , the peptide inhibiting tyrosine phosphorylation of the α v β 3  integrin. 
     
     
         19 : The pharmaceutical composition of  claim 16 , the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation. 
     
     
         20 : The pharmaceutical composition of  claim 16 , the peptide competing with α v β 3  integrin for interaction with VEGFR2. 
     
     
         21 : The pharmaceutical composition of  claim 16 , the synthetic peptide further comprises a transport moiety that facilitates transport of the synthetic peptide into a cell. 
     
     
         22 : The pharmaceutical composition of  claim 16 , the amino acid sequence is selected from the group consisting of: SEQ ID NO: 6, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17. 
     
     
         23 : A pharmaceutical composition comprising: a synthetic peptide, the peptide comprises an amino acid sequence substantially homologous to about 5 to about 30 consecutive amino acids of a portion of the cytoplasmic domain of α v β 3  integrin that includes a tyrosine residue, the amino acid sequence of the peptide including a γ-carboxyglutamic acid residue that substitutes a corresponding tyrosine residue of the portion of the cytoplasmic domain of α v β 3  integrin, the peptide is about 10 to about 50 amino acids in length, and the peptide inhibits interaction of α v β 3  integrin with VEGFR2. 
     
     
         24 : The pharmaceutical composition of  claim 23 , the peptide not inhibiting natural ligand binding to the α v β 3  integrin. 
     
     
         25 : The pharmaceutical composition of  claim 23 , the peptide inhibiting tyrosine phosphorylation of the α v β 3  integrin. 
     
     
         26 : The pharmaceutical composition of  claim 23 , the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation. 
     
     
         27 : The pharmaceutical composition of  claim 23  the peptide competing with α v β 3  integrin for interaction with VEGFR2. 
     
     
         28 : The pharmaceutical composition of  claim 23 , the synthetic peptide further comprises a transport moiety that facilitates transport of the synthetic peptide into a cell.