Abstract: Peptide analogs the high molecular weight kininogen domain 3 are potent inhibitors of angiogenesis. The peptides have the formula (a) X1-Asn-Asn-Ala-Thr-Phe-Tyr-Phe-Lys-X2, (b) X3-Cys-Val-Gly-Cys-X4, (c) X5-Leu-Asp-X7-Asn-Ala-Glu-Val-Tyr-X6, or (d) Tyr-Phe-Ile-Asp-Phe-Val-Ala-Arg-Glu-Thr-Thr-X7-Ser-Lys-Glu-Ser wherein: X1, X2, X3, X4, X5, and X6 are from zero to twelve amino acids, independently the same or different, more preferably from zero to six amino acids, and; X7 is Ala or Cys. The peptides may also comprise biologically active fragments of high molecular weight kininogen domain 3. Methods of inhibiting endothelial cell proliferation and angiogenesis are provided.

Abstract: Two-chain high molecular weight kininogen, and peptide analogs thereof having homology to sites within kininogen domain 5, are potent inhibitors of angiogenesis. The peptides have the formula X1-His-Lys-X-Lys-X2 wherein X is any amino acid, X1 is from zero to twelve amino acids, more preferably from zero to six amino acids, most preferably from zero to three amino acids, and X2 is from zero to twelve amino acids, more preferably from zero to six amino acids, most preferably from zero to three amino acids. X is preferably an amino acid having a nonpolar side chain, or a polar side chain which is uncharged at pH 6.0 to 7.0. X is most preferably Asn, Phe or His. Methods of inhibiting endothelial cell proliferation and angiogenesis are provided.