Polymers containing multivalent amyloid-beta-binding D-peptides and their use
View Patent ↗The invention relates to novel multivalent polymeric amyloid-beta-binding substances composed of several interconnected substances which per se already have amyloid-beta-binding properties, and to the use of these substances, referred to hereinbelow as “polymers”, in particular in medicine.
1. A polymer which comprises at least two units which bind to amyloid-beta oligomers, wherein at least one of the at least two units is selected from SEQ ID NO:1, and homologs of this unit.
2. The polymer of claim 1 , wherein at least one other of the at least two units is selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, and homologs of the above-described units.
3. The polymer of claim 1 , wherein the at least two units are identical or nonidentical.
4. The polymer of claim 1 , wherein the polymer comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more units which bind to amyloid-beta oligomers.
5. The polymer of claim 1 , wherein the at least two units are peptides essentially composed of D-amino acids or antibodies or antibody fragments which bind to amyloid-beta.
6. The polymer of claim 1 , wherein the at least two units are covalently or noncovalently linked to each other.
7. The polymer of claim 1 , wherein the at least two units are linked to each other directly.
8. The polymer of claim 1 , wherein the at least two units are linked to each other via a linker group.
9. The polymer of claim 1 , wherein the at least two units are linked to each other in a linear or branched fashion.
10. The polymer of claim 1 , wherein the polymer is a dendrimer and/or wherein the at least two units are linked to a platform molecule.
11. The polymer of claim 1 , wherein each of the at least two units binds to a monomer and/or oligomer and/or fibrils of the amyloid-beta peptide with a dissociation constant (K D value) of not more than 500 μM.
12. The polymer of claim 1 , wherein each of the at least two units binds to a monomer and/or oligomer and/or fibrils of the amyloid-beta peptide with a dissociation constant (K D value) of not more than 4 μM.
13. The polymer of claim 1 , wherein the polymer binds amyloid-beta oligomers with a dissociation constant of not more than 1 μM.
14. The polymer of claim 13 , wherein the polymer binds amyloid-beta oligomers with a dissociation constant of not more than 20 pM.
15. A pharmaceutical composition which comprises the polymer of claim 1 .
16. A pharmaceutical composition which comprises the polymer of claim 13 .
17. A kit, probe or composition which comprises the polymer of claim 1 .
18. A process for preparing the polymer of claim 1 , wherein the process comprises a peptide synthesis method or an organic synthesis method for low-molecular-weight compounds or wherein the polymer is prepared via a recombinant production of proteins.