AGER-peptides and use thereof
View Patent ↗The present invention relates to the identification, functionality and use of domains from the N terminus of the receptor for Advanced Glycation End Products (AGER). These domains, called receptor multimerization epitope (RME), are highly conserved in all AGER protein sequences. They represent the mediators for AGER self-association and heteromerization with other proteins. The invention likewise relates to the identification, functionality and use of peptides derived from the C domain of AGER (AGER-CDP). The AGER RMEs and AGER-CDPs of the invention are suitable as target for identifying AGER ligands which modulate the natural ligand interaction; as immunogen for active or passive immunization of individuals, as diagnostic means for identifying immunogenic reactions, and as peptide ligands for modulating protein-protein interactions involving AGER.
1. A hybrid protein comprising a) a peptide fragment of the C domain of the receptor for advanced glycation endproducts (AGER-CDP), which is a length of about 30 to about 50 amino acid residues, wherein said AGER-CDP comprises a sequence selected from the group consisting of
DGKPLVPNEKGVSVKEQTRRHPETGLFTLQ,
(SEQ ID NO: 31)
TLQSELMVTPARGGDPRPTFSCSFSPGLPR,
(SEQ ID NO: 32)
and
LPRHRALRTAPIQPRVWEPVPLEEVQLVVE;
(SEQ ID NO: 33)
and b) a heterologous protein or protein fragment.
2. The hybrid protein according to claim 1 , additionally comprising a functional part of a protein selected from immunglobulins and fragments thereof.
3. The hybrid protein according to claim 1 , comprising an Ig Fc fragment functionally linked to the AGER-CDP.
4. An AGER-CDP derivative comprising the hybrid protein according to claim 1 in PEGylated form or coupled to a marker.
5. The hybrid protein according to claim 1 , wherein the AGER-CDP is in the form of a cyclic peptide.
6. A pharmaceutical composition comprising in a pharmaceutically acceptable carrier at least one active ingredient selected from the hybrid protein according to claim 1 and a nucleic acid sequence coding for said hybrid protein.
7. The pharmaceutical composition according to claim 6 , additionally comprising as active ingredient an active substance selected from:
a) neurotrophic factors, inosine, neuroimmunophilins, chondroitin sulfate proteoglycan-degrading enzymes;
b) antibodies against neurite growth inhibitors, Nogo-A, MAG, Omgp, and/or their receptors,
c) soluble NgR fragment, Nogo-A peptide fragments,
d) inhibitors of the p75-mediated signal cascade, and
e) cAMP and functional analogs, protein kinase A, arginase I, polyamines, ciliary neurotrophis factor.
8. The pharmaceutical composition according to claim 6 , for intrathecal, intravenous, subcutaneous, oral, parenteral, nasal or inhalational administration.
9. An immunogen comprising hybrid protein according to claim 1 , in a pharmaceutically acceptable carrier and optionally with an adjuvant for active immunization.