Peptides that bind to the heparin binding domian of vegf and vegfr-2

1 . A peptide of the amino acid sequence of formula (I)

Z 1 -X 1 —X 2 —X 3 —X 4 —X 5 -Gly-X 7 —X 8 —X 9 -Z 2 -Y 1   (I)

or formula (II)

Z 1 -X 1 -Tyr-X 3 (-Ala or Ser)-Asp-Gly-X 7 -(Tyr or Phe)-Asp-Z 2 -Y 1   (II)

wherein

X 1 is an amino acid selected from the group Ser, His, Thr, Ala, Gln, Phe, Gly and Ile

X 2 is an amino acid selected from the group Tyr, Arg and Phe

X 3 is an amino acid selected from the group Tyr, Ser, Asn, Glu, Asp and Thr

X 4 is an amino acid selected from the group Ser, Ala, Gly, Asp and Phe

X 5 is an amino acid selected from the group Asp and Ser,

X 7 is an amino acid selected from the group Thr, Val, Met, Ser, Trp, Tyr, Leu and Ala

X 8 is an amino acid selected from the group Tyr, Phe and Leu

X 9 is an amino acid selected from the group Asp, Ser and Glu

Z 1 represent an amino acid residue capable of forming a disulphide bond, preferably a cysteine or a homocysteine residue, or a residue capable of forming a thioether preferably the residue is Q-C(═O) wherein Q represents —CH 2 ) n or —CH 2 ) n —C 6 H 4 where n represents a positive integer 1 to 10 or is absent and

Z 2 represent an amino acid residue capable of forming a disulphide bond, preferably a cysteine or a homocysteine residue or is absent

Y 1 represents 1-10 amino acids or is absent

or pharmaceutically acceptable salts thereof.

2 . A peptide according to claim 1 of the amino acid sequence

(SEQ ID NO 1)

Cys-Ser-Tyr-Tyr-Ser-Asp-Gly-Val-Tyr-Asp-Cys,,

(SEQ ID NO 2)

Cys-His-Tyr-Ser-Ser-Asp-Gly-Thr-Tyr-Asp-Cys,,

(SEQ ID NO 3)

Cys-Thr-Tyr-Asn-Gly-Asp-Gly-Ser-Phe-Asp-Cys,,

(SEQ ID NO 4)

Cys-Ala-Tyr-Glu-Ala-Asp-Gly-Trp-Phe-Asp-Cys,,

(SEQ ID NO 5)

Cys-Ser-Tyr-Ser-Ala-Asp-Gly-Thr-Leu-Asp-Cys,,

(SEQ ID NO 6)

Cys-Gln-Tyr-Asp-Ser-Ser-Gly-Met-Tyr-Asp-Cys,,

(SEQ ID NO 7)

Cys-Phe-Phe-Asp-Ser-Ser-Gly-Tyr-Phe-Asp-Cys,,

(SEQ ID NO 8)

Cys-Thr-Tyr-Ser-Ala-Asp-Gly-Leu-Tyr-Asp-Cys,,

(SEQ ID NO 9)

Cys-His-Phe-Asp-Gly-Asp-Gly-Ser-Tyr-Asp-Cys,,

(SEQ ID NO 10)

Cys-Thr-Tyr-Glu-Pro-Ser-Gly-Met-Tyr-Asp-Cys,,

(SEQ ID NO 11)

Cys-Gln-Tyr-Thr-Ala-Asp-Gly-Ala-Phe-Asp-Cys,,

(SEQ ID NO 12)

Cys-Ile-Tyr-Glu-Ser-Asp-Gly-Met-Phe-Ser-Cys,,

(SEQ ID NO 13)

Cys-Gly-Arg-Ser-Asp-Gly-Thr-Trp-Tyr-Glu-Cys,

or

(SEQ ID NO 14)

Cys-Ser-Tyr-Tyr-Ala-Asp-Gly-Met-Tyr-Ser-Cys,.

3 . A targetable diagnostic and/or therapeutically active agent of formula (III)

V-L-Z  Formula (III)

wherein the vector V is a peptide according to claim 1

L represents a bond, a spacer or a linker and

Z represents an antineoplastic agent, a reporter moiety or a group that optionally can carry an imaging moiety M.

4 . An agent as claimed in claim 3 where Z is a chelating agent of Formula IV

where:

each R 1 , R 2 , R 3 and R 4 is independently an R group;

each R group is independently H or C 1-10 alkyl, C 3-10 alkylaryl, C 2-10 alkoxyalkyl, C 1-10 hydroxyalkyl, C 1-10 alkylamine, C 1-10 fluoroalkyl, or 2 or more R groups, together with the atoms to which they are attached form a carbocyclic, heterocyclic, saturated or unsaturated ring.

5 . An agent as claimed in claim 3 wherein Z comprises a reporter moiety, M wherein the reporter moiety M comprises metal radionuclides, paramagnetic metal ions, fluorescent metal ions, heavy metal ions or cluster ions.

6 . An agent as claimed in claim 5 wherein the reporter moiety M comprises 90 Y, 99m Tc, 111 In, 47 Sc, 67 Ga, 51 Cr, 177m Sn, 67 Cu, 167 Tm, 97 Ru, 188 Re, 177 Lu, 199 Au, 203 Pb, 141 Ce, or 18 F.

7 . An agent as claimed in claim 3 where each reporter (Z) can carry a multiplicity of vectors V.

8 . An agent as claimed in claim 3 where the antineoplastic agent Z represent cyclophosphamide, chloroambucil, busulphan, methotrexate, cytarabine, fluorouracil, vinblastine, paclitaxel, doxorubicin, daunorubicin, etoposide, teniposide, cisplatin, amsacrine or docetaxel.

9 . A pharmaceutical composition comprising an effective amount of a compound of general Formula (III) or a salt thereof, together with one or more pharmaceutically acceptable adjuvants, excipients or diluents for use in enhancing image contrast in in vivo imaging or for treatment of a disease.

10 . A method of generating enhanced images of a human or animal body previously administered with a contrast agent composition comprising a compound as claimed in claim 3 , which method comprises generating an image of at least part of said body.