Binding compounds, immunogenic compounds and peptidomimetics

1. A peptidomimetic consisting of a polypeptide attached to a scaffold wherein:

i) the polypeptide is the amino acid sequence of a cysteine-knot growth factor family member from position CysIV+x to position CysV+y, wherein −5≦x≦1 and 1≦y≦6, with the proviso that x+y=−1, 0, 1 or 2,

wherein two amino acid residues in said amino acid sequence have been replaced by a cysteine residue,

wherein the first cysteine residue is introduced at position CysIV+p, which is located p residues C-terminal from CysIV, wherein 5≦p≦12,

wherein the second cysteine residue is introduced at position CysV−q, which is located q residues N-terminal from CysV, wherein 4≦q≦12,

wherein (p−q) is −3, −2, −1, 0, 1, 2 or 3, and

wherein the first and second introduced cysteine residues are attached to each other via the scaffold,

wherein cysteine residues in the amino acid sequence other than said first and second introduced cysteine residues are optionally replaced by an amino acid residue that is not reactive with the scaffold; and

ii) wherein the scaffold is an aromatic molecule with at least two halomethyl substituents.

2. The peptidomimetic of claim 1 , wherein the amino acid sequence is from CysIV+1 to CysV+1, from CysIV−5 to CysV+6, from CysIV−3 to CysV+4, from CysIV−5 to CysV+4 or from CysIV−2 to CysV+4.

3. The peptidomimetic of claim 1 , wherein the position of the first and second introduced cysteines correspond to positions CysIV+12 and CysV−10, or to CysIV+11 and CysV−10, CysIV+10 and CysV−8, CysIV+9 and CysV−8, CysIV+8 and CysV−6, CysIV+7 and CysV−5, CysIV+7 and CysV−6, CysIV+7 and CysV−4, CysIV+5 and CysV−4 or CysIV+6 and CysV−4, respectively.

4. The peptidomimetic of claim 3 , wherein the position of the first and second introduced cysteines correspond to positions CysIV+10 and CysV−8, respectively.

5. The peptidomimetic of claim 1 , wherein the scaffold is selected from the group consisting of ortho-, meta- and para-dihalomethylbenzene, and 1,2,4,5 tetra halomethylbenzene.

6. The peptidomimetic of claim 1 , wherein the amino acid sequence is from CysIV+1 to CysV+1 and wherein the scaffold is meta-1,3-bis(bromomethyl)benzene (m-T2).

7. The peptidomimetic of claim 1 , wherein the amino acid sequence is from CysIV−2 to CysV+4 and wherein the scaffold is 1,2,4,5-tetra(bromomethyl)benzene (T4).

8. The peptidomimetic of claim 1 , wherein the member of the cysteine-knot protein family is a member of the glycoprotein hormone-beta (GLHB) subfamily, the platelet-derived growth factor (PDGF) subfamily, the transforming growth factor (TGF) subfamily, the nerve growth factor (NGF) subfamily or the glycoprotein hormone-alpha (GLHA) subfamily.

9. The peptidomimetic of claim 1 , wherein the position of said first introduced cysteine corresponds to amino acid position CysIV+10 and the position of the second introduced cysteine corresponds to position CysV−8, and wherein said member of the cystine-knot protein family is a member of the GLHB subfamily, the PDGF subfamily or the TGF subfamily.

10. The peptidomimetic of claim 3 , wherein the position of the first introduced cysteine corresponds to amino acid position CysIV+8 and wherein the position of the second introduced cysteine corresponds to position CysV−6.

11. The peptidomimetic of claim 3 , wherein the position of the first introduced cysteine corresponds to amino acid position CysIV+7 and wherein the position of the second introduced cysteine corresponds to position CysV−6.

12. The peptidomimetic of claim 1 , wherein the position of the first introduced cysteine corresponds to amino acid position CysIV+8 and the position of the second introduced cysteine corresponds to position CysV−6, wherein the member of the cystine-knot growth factor protein family is a VEGF protein.

13. A peptidomimetic selected from the group consisting of

the polypeptide TFKELVYETCRVPGAAHHADSLCTYPVATQAH (SEQ ID NO:31) attached to the scaffold m-T2, the polypeptide KIQKTATFKELVYETCRVPGAAHHADSLCTYPVATQAHAGK (SEQ ID NO:32) attached to the scaffold T4, the polypeptide TFKCLVYETVRVPGAAHHADSLYTYPVACQAH (SEQ ID NO:37) attached to the scaffold m-T2, the polypeptide TFKELVYETCRVPGDAHHADSLCTYPVATQAH (SEQ ID NO:38) attached to the scaffold m-T2, the polypeptide TFKELVYETCRVPGAAHHADSLCTYPVATQAH (SEQ ID NO:31) attached to the scaffold T3, the polypeptide TFKELVYETCRVPGDAHHADKLCTYPVATQAH (SEQ ID NO:40) attached to the scaffold m-T2, the polypeptide TFKELVYETCRVPGDAHKAIDSLCTYPVATQAH (SEQ ID NO:41) attached to the scaffold m-T2, the polypeptide ESNCTMQIMRIKPHQGQHIGEMSCLQH (SEQ ID NO: 42) attached to the scaffold m-T2, the polypeptide EESNCTMQIMRIKPHQGQHIGEMSCLQHN (SEQ ID NO:43) attached to the scaffold m-T2, the polypeptide NYRDVRFESCRLPGAPRGVNPVCSYAVALSAQ (SEQ ID NO: 126) attached to the scaffold m-T2, the polypeptide VVANYRDVRFESCRLPGAPRGVNPVCSYAVALSAQAAL (SEQ ID NO:35) attached to the scaffold m-T2, and

a dimer of the polypeptide

NYRDVRFESCRLPGCPRGVNPVCSYAVALSAQ

(SEQ ID NO:44) wherein the monomers are joined by a disulfide bond between the cysteine at position 15 in each monomer and wherein each monomer is individually attached to the scaffold m-T2;

wherein the scaffold m-T2 is meta-1,3-bis(bromomethyl)benzene, the scaffold T3 is 2,4,6-tris(bromomethyl)mesitylene and the scaffold T4 is 1,2,4,5-tetra(bromomethyl)benzene; and

wherein in each peptidomimetic the two cysteines of the polypeptide are attached via the scaffold.

14. A method for preparing a peptidomimetic of claim 1 , comprising:

providing said polypeptide and scaffold, and

contacting said polypeptide and scaffold under conditions that allow for the covalent attachment of said polypeptide to said scaffold.

15. A composition comprising the peptidomimetic of claim 1 .

16. The composition of claim 15 , wherein the peptidomimetic is coupled to a carrier.

17. The peptidomimetic of claim 5 , wherein said scaffold is selected from the group consisting of meta-1,3-bis(bromomethyl)benzene (m-T2) and 1,2,4,5-tetra(bromomethyl)benzene (T4).