ADDL receptor polypeptides, polynucleotides and host cells for recombinant production
This invention provides a novel receptor expressed on neuronal cells in a developmentally-specific manner. Accordingly, this invention provides the amino acid sequences of selected portions of the receptor and polynucleotides encoding these portions as well as antibodies that bind to the polypeptide portions of the receptor. Compositions and methods for using the compositions are also provided.
1. An antibody that binds an amyloid β-derived diffusible ligand receptor polypeptide, said polypeptide comprising amino acid sequences selected from the group consisting of:
(a)
CTENVPVTDFFVGPVCIIPK
(SEQ ID NO: 5)
and
(b)
SSVWDERHDSHIPLEDCR
(SEQ ID NO: 6).
2. An antibody that binds two binding regions of an amyloid β-derived diffusible ligand receptor polypeptide, the two binding regions being non-contiguous
wherein the first binding region is selected from the group of amino acid sequences consisting of:
(a)
CTENVPVTDFFVGPVCIIPK;
(SEQ ID NO: 5)
(b)
SSVWDERHDSHIPLEDCR;
(SEQ ID NO: 6)
and
(c)
HDSHIPLEDCR;
(SEQ ID NO: 7)
and wherein the second binding region is different from the first binding region and is selected from the group of amino acid sequences consisting of:
(d)
AVIMFANEDDIR;
(SEQ ID NO: 2)
(e)
ASIDGFDQYFRSQTLANNR;
(SEQ ID NO: 3)
(f)
ASIDGFDQYFR;
(SEQ ID NO: 4)
(g)
CTENVPVTDFFVGPVCIIPK;
(SEQ ID NO: 5)
(h)
SSVWDERHDSHIPLEDCR;
(SEQ ID NO: 6)
and
(i)
HDSHIPLEDCR
(SEQ ID NO: 7).
3. An antibody that binds at least one amyloid β-derived diffusible ligand receptor polypeptide selected from the group consisting of:
(a) CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5);
(b) SSVWDERHDSHIPLEDCR (SEQ ID NO: 6); and
(c) HDSHIPLEDCR (SEQ ID NO: 7);
wherein the antibody optionally further binds to at least one polypeptide selected from the group consisting of
AVIMFANEDDIR (SEQ ID NO: 2),
ASIDGFDQYFRSQTLANNR (SEQ ID NO: 3) and
ASIDGFDQYFR (SEQ ID NO: 4).
4. A biologically active fragment of the antibody of claim 1 , 2 or 3 .
5. The antibody of claim 4 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, a chimeric antibody or a humanized antibody.
6. A composition comprising the antibody of claim 1 , 2 or 3 and a carrier.
7. A composition comprising the biologically active fragment of claim 4 and a carrier.
8. An isolated antibody-peptide complex comprising an antibody of any one of claim 1 , 2 or 3 and a polypeptide that specifically binds to the antibody.
9. The isolated complex of claim 8 , wherein the polypeptide is the polypeptide against which the antibody is raised.
10. The isolated complex of claim 8 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, a chimeric antibody or a humanized antibody.
11. An isolated antibody that inhibits binding of soluble amyloid β-derived diffusible ligand to a neural receptor and binds a polypeptide selected from the group consisting of:
(a) a polypeptide comprising amino acid sequence CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5) and SSVWDERHDSHIPLEDCR (SEQ ID NO: 6);
(b) a polypeptide comprising two non-contiguous binding regions, the binding regions comprising ASIDGFDQYFRSQTLANNR (SEQ ID NO: 3) and SSVWDERHDSHIPLEDCR (SEQ ID NO: 6); and
(c) a polypeptide comprising two non-contiguous binding regions, the binding regions comprising ASIDGFDQYFR (SEQ ID NO: 4) and HDSHIPLEDCR (SEQ ID NO: 7).
12. The antibody of claim 11 , wherein the antibody binds two or more polypeptides of the group consisting of (a), (b) and (c).
13. A composition comprising an antibody of claim 11 or 12 and a carrier.
14. The composition of claim 13 , wherein the carrier is a solid support.
15. The composition of claim 13 , wherein the carrier is a pharmaceutically acceptable carrier.
16. An antibody that binds an amyloid β-derived diffusible ligand receptor polypeptide selected from the group consisting of:
(a)
CTENVPVTDFFVGPVCIIPK;
(SEQ ID NO: 5)
(b)
SSVWDERHDSHIPLEDCR;
(SEQ ID NO: 6)
and
(c)
HDSHIPLEDCR
(SEQ ID NO: 7).
17. A biologically active fragment of the antibody of claim 16 .
18. The antibody of claim 16 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, a chimeric antibody or a humanized antibody.
19. A composition comprising the antibody of claim 16 and a carrier.
20. A composition comprising the biologically active fragment of claim 17 and a carrier.
21. An isolated antibody-peptide complex comprising an antibody of claim 16 and a polypeptide that specifically binds to the antibody.
22. The isolated complex of claim 21 , wherein the polypeptide is the polypeptide against which the antibody is raised.
23. The isolated complex of claim 21 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, a chimeric antibody or a humanized antibody.
24. An isolated antibody that inhibits binding of soluble amyloid β-derived diffusible ligand to a neural receptor and binds a polypeptide selected from the group consisting of:
(a) a polypeptide comprising the amino acid sequence CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5);
(b) a polypeptide comprising the amino acid sequence SSVWDERHDSHIPLEDCR (SEQ ID NO: 6); and
(c) a polypeptide comprising the amino acid sequence HDSHIPLEDCR (SEQ ID NO: 7).
25. A composition comprising an antibody of claim 24 and a carrier.
26. The composition of claim 25 , wherein the carrier is a solid support.
27. The composition of claim 25 , wherein the carrier is a pharmaceutically acceptable carrier.