JNK inhibitor molecules
JNK inhibitor molecules are described. In addition, methods for raising antibodies against such JNK inhibitor molecules are disclosed. These antibodies and cells producing these antibodies are also described.
1. A JNK inhibitor comprising an inhibitory polypeptide sequence sharing at least 80% sequence identity with SEQ ID NO: 8.
2. The JNK inhibitor according to claim 1 , wherein the inhibitory polypeptide sequence is SEQ ID NO: 8.
3. The JNK inhibitor of claim 1 , wherein the inhibitory polypeptide sequence sharing at least 80% sequence identity with SEQ ID NOs: 8 has a D-Ala residue at a position corresponding to position 6 of SEQ ID NO: 8.
4. The JNK inhibitor of claim 1 , wherein the JNK inhibitor further comprises a transporter sequence.
5. The JNK inhibitor according to claim 4 , wherein the inhibitory polypeptide sequence and the transporter sequence overlap.
6. The JNK inhibitor according to claim 4 , wherein the transporter sequence comprises a sequence of alternating D- and L-amino acids according to anyone of SEQ ID NOs: 28-30.
7. The JNK inhibitor of claim 4 , wherein said transporter sequence is SEQ ID NO: 46.
8. The JNK inhibitor of claim 4 , wherein said transporter sequence is selected from any one of SEQ ID NOs: 31-34, 46, 47 and 52-151.
9. The JNK inhibitor of claim 4 , wherein said transporter sequence is positioned directly N-terminal or directly C-terminal of the inhibitory polypeptide sequence.
10. The JNK inhibitor of claim 4 , wherein the JNK inhibitor comprises a sequence selected from SEQ ID NOs: 171-173, 176-177 and 182-187.
11. The JNK inhibitor of claim 4 , wherein the JNK inhibitor comprises the sequence of SEQ ID NO: 172.
12. The JNK inhibitor of claim 1 , wherein the L arginine (R) residue at position 4 and the L-leucine (L) residue at positions 8 and 10 of SEQ ID NO: 8 cannot be changed, and wherein at least one other amino acid of the inhibitory polypeptide sequence is in the D conformation.
13. The JNK inhibitor of claim 12 , wherein the amino acid corresponding to position 1 of SEQ ID NO: 8 is selected from the group consisting of R, P, Q and r, the amino acid corresponding to position 2 of SEQ ID NO: 8 is selected from the group consisting of R, P, G and r, the amino acid corresponding to position 3 of SEQ ID NO: 8 is selected from the group consisting of K, R, k and r, the amino acid corresponding to position 5 of SEQ ID NO: 8 is selected from the group consisting of P and K, the amino acid corresponding to position 6 of SEQ ID NO: 8 is absent or is selected from the group consisting of T, a, s, q, k, the amino acid corresponding to position 7 of SEQ ID NO: 8 is selected from the group consisting of T, D and A, the amino acid corresponding to position 9 of SEQ ID NO: 8 is selected from the group consisting of N, n, r and K, and the amino acid corresponding to position 11 of SEQ ID NO: 8 is selected from the group consisting of F, f and w, wherein an amino acid residue in a capital letter indicates an L-amino acid, and an amino acid residue in a lower case letter indicates a D amino acid residue.
14. The JNK inhibitor of claim 1 , wherein the inhibitory polypeptide sequence sharing at least 80% sequence identity with SEQ ID NOs: 8 has a D-Lys residue at a position corresponding to position 3 of SEQ ID NO: 8.
15. The JNK inhibitor of claim 1 , wherein the inhibitory polypeptide sequence sharing at least 80% sequence identity with SEQ ID NOs: 8 has a D-Phe residue at a position corresponding to position 11 of SEQ ID NO: 8.