Anti-angiogenic peptides and uses thereof

Abstract

Provided are peptide sequences derived from prostate serum antigen (PSA). The peptides are provided in cyclic and linear form. Methods for using the peptides for inhibition of angiogenesis, such as angiogenesis in a tumor, are provided.

We claim: 
     
         1 . A peptide having a sequence selected from Lys Asn Arg Phe Leu Arg Pro Gly Asp Asp Ser Ser His (SEQ ID NO:1), Cys Lys Asn Arg Phe Leu Arg Pro Gly Asp Asp Ser Ser His Cys (SEQ ID NO:7), Asn Asp Val Cys Ala Gln Val His Pro Gln Lys Val Thr Lys (SEQ ID NO:3), Val Ala Ala Gln Val His Pro Gln Lys Val Thr Lys (SEQ ID NO:8), Asn Asp Val Cys Ala Gln Val His Pro Gln Lys Val Thr Lys Phe Met Leu Cys Ala (SEQ ID NO:6), and Asn Asp Val Ala Ala Gln Val His Pro Gln Lys Val Thr Lys Phe Met Leu Ala Ala (SEQ ID NO:9). 
     
     
         2 . The peptide of  claim 1 , wherein the peptide is cyclic. 
     
     
         3 . The peptide of  claim 2 , wherein the peptide has the sequence of SEQ ID NO:6, and wherein the two Cys in the sequence of SEQ ID NO:6 are connected to one another via a disulfide bond, or wherein the peptide has the sequence of SEQ ID NO:7, and wherein the two Cys in the sequence of SEQ ID NO:7 are connected to one another via a disulfide bond. 
     
     
         4 . The peptide of  claim 1 , wherein the peptide comprises one, two, three, or four conservative amino acid substitutions, and wherein the peptide is capable of inhibiting tubule formation by human umbilical vein endothelial cells. 
     
     
         5 . The peptide of  claim 1 , wherein the peptide is present in a composition comprising a pharmaceutically acceptable carrier. 
     
     
         6 . The peptide of  claim 5 , wherein the peptide is cyclic. 
     
     
         7 . The composition of  claim 6 , wherein the isolated peptide has the sequence of SEQ ID NO:6, and wherein the two Cys in the sequence of SEQ ID NO:6 are connected to one another via a disulfide bond, or wherein the isolated peptide has the sequence of SEQ ID NO:7, and wherein the two Cys in the sequence of SEQ ID NO:7 are connected to one another via a disulfide bond. 
     
     
         8 . A method of inhibiting angiogenesis in an individual comprising administering a composition comprising a peptide of  claim 1  to an individual in an amount effective to inhibit the angiogenesis in the individual. 
     
     
         9 . The method of  claim 8 , wherein the inhibition of angiogenesis comprises inhibition of angiogenesis in a tumor in the individual. 
     
     
         10 . The method of  claim 8 , wherein the peptide is cyclic. 
     
     
         11 . The method of  claim 10 , wherein the peptide has the sequence of SEQ ID NO:6, and wherein the two Cys in the sequence of SEQ ID NO:6 are connected to one another via a disulfide bond, or wherein the isolated peptide has the sequence of SEQ ID NO:7, and wherein the two Cys in the sequence of SEQ ID NO:7 are connected to one another via a disulfide bond. 
     
     
         12 . The method of  claim 8 , wherein the composition comprises more than one peptide of  claim 1 . 
     
     
         13 . A method of inhibiting human endothelial cell migration comprising contacting human endothelial cells with a composition comprising a peptide of  claim 1 , wherein the migration is inhibited subsequent to the contacting of the human endothelial cells with the composition. 
     
     
         14 . The method of  claim 13 , wherein the peptide is cyclic. 
     
     
         15 . The method of  claim 14 , wherein the peptide has the sequence of SEQ ID NO:6, and wherein the two Cys in the sequence of SEQ ID NO:6 are connected to one another via a disulfide bond, or wherein the isolated peptide has the sequence of SEQ ID NO:7, and wherein the two Cys in the sequence of SEQ ID NO:7 are connected to one another via a disulfide bond.