CGRP binding nucleic acids
The invention relates to an antagonist for CGRP and amylin, whereby the antagonist is a nucleic acid and said nucleic acid binds to CGRP or amylin. Said nucleic acid preferably comprises an L-nucleotide.
1. An antagonist of CGRP, wherein the antagonist is an L-nucleic acid which binds to CGRP with a K D of less than 100 nM, wherein said L-nucleic acid comprises SEQ ID NO:246 or an L-nucleic acid at least 85% homologous thereto.
2. The antagonist of CGRP as claimed in claim 1 , wherein the CGRP is α-CGRP.
3. The antagonist as claimed in claim 1 , wherein the CGRP is β-CGRP.
4. An antagonist of the CGRP receptor, wherein the antagonist is an L-nucleic acid which binds to a ligand of the receptor with a K D of less than 100 nM, wherein said L-nucleic acid comprises SEQ ID NO:246 or an L-nucleic acid at least 85% homologous thereto.
5. The antagonist as claimed in claim 4 , wherein the ligand is α-CGRP.
6. The antagonist as claimed in claim 4 , wherein the ligand is β-CGRP.
7. An L-nucleic acid which binds to CGRP with a K D of less than 100 nM, wherein said L-nucleic acid comprises SEQ ID NO:246 or an L-nucleic acid at least 85% homologous thereto.
8. The nucleic acid as claimed in claim 7 , wherein the CGRP is α-CGRP.
9. The nucleic acid as claimed in claim 7 , wherein the CGRP is β-CGRP.
10. The nucleic acid as claimed in claim 7 , wherein the nucleic acid is selected from the group consisting of DNA, RNA and combinations thereof.
11. The nucleic acid as claimed in claim 7 , wherein the K D value of the nucleic acid is selected from the group consisting of less than 0.05 μM and less than 0.01 μM.
12. The nucleic acid as claimed in claim 7 , wherein the K D value of the nucleic acid is selected from the group consisting of more than 10 nM, more than 1 nM and more than 0.01 nM.
13. The nucleic acid as claimed in claim 7 , wherein the nucleic acid comprises a minimal binding motif.
14. The nucleic acid as claimed in claim 7 , wherein said nucleic acid has a length selected from the group consisting of 15 to 150 nucleotides, 20 to 100 nucleotides, 20 to 80 nucleotides, 20 to 60 nucleotides, 20 to 50 nucleotides and 30 to 50, and 25 to 45 nucleotides.
15. The nucleic acid as claimed in claim 7 , wherein the nucleic acid has a two-, three- or multi-partite structure.
16. A method of inhibiting CGRP, the CGRP receptor system or both comprising exposing CGRP or a CGRP receptor system to the nucleic acid as claimed in claim 7 .
17. A composition comprising the nucleic acid of claim 7 , 8 or 9 and a pharmaceutically acceptable carrier.
18. A complex comprising CGRP and the nucleic acid of claim 7 , 8 or 9 .
19. The antagonist of CGRP of claim 1 , wherein said L-nucleic acid is at least 90% homologous to SEQ ID NO:246.
20. The antagonist of CGRP of claim 19 , wherein said L-nucleic acid is at least 95% homologous to SEQ ID NO:246.
21. The antagonist of the CGRP receptor of claim 4 , wherein said L-nucleic acid is at least 90% homologous to SEQ ID NO:246.
22. The antagonist of the CGRP receptor of claim 21 , wherein said L-nucleic acid is at least 95% homologous to SEQ ID NO:246.
23. The L-nucleic acid of claim 7 , wherein said L-nucleic acid is at least 90% homologous to SEQ ID NO:246.
24. The L-nucleic acid of claim 23 , wherein said L-nucleic acid is at least 95% homologous to SEQ ID NO:246.
25. The nucleic acid of claim 13 , where said motif comprises the sequence, GGACUGAUGGCGCGGUCCUAUUACGCCGAXDAGGGWGWGGGGR (SEQ ID NO:286), wherein X is G or absent; D is G, U or A; W is A or U and R is G or A.