Screening Assays, Modulators and Modulation of Activation of Receptor for Advanced Glycation End-Products (RAGE)

An isolated or purified peptide that inhibits RAGE ligand-independent signalling, the peptide:

• (i) comprising an amino acid sequence that is at least 90% identical to a fragment of residues 22 to 404 of wild-type RAGE as set forth in SEQ ID NO:
• 14, wherein the peptide comprises at least both residues 379 and 391, and wherein the residue at 379 is not Q or a conservative amino acid substitution thereof;
• (ii) consisting of an amino acid sequence that is greater than 90% identical to a fragment of residues 22 to 404 of wild-type RAGE as set forth in SEQ ID NO:
• 14, wherein the peptide comprises at least both residues 379 and 391,
• wherein the residue at 379 is not Q or a conservative amino acid substitution thereof, or
• wherein the residue at 391 is not S or a conservative amino acid substitution thereof;
• (iii) comprising an amino acid sequence that is at least 95% identical to a fragment of residues 22 to 404 of wild-type RAGE as set forth in SEQ ID NO:
• 14, wherein the peptide comprises at least both residues 379 and 391,
• wherein the residue at 379 is not Q or a conservative amino acid substitution thereof, or
• wherein the residue at 391 is not S or a conservative amino acid substitution thereof;
• (iv) comprising an amino acid sequence that is at least 90% identical to a fragment of residues 22 to 404 of wild-type RAGE as set forth in SEQ ID NO:
• 14, wherein the peptide comprises at least both residues 379 and 391,
• wherein the residue at 379 is Q or a conservative amino acid substitution thereof, and the residue 391 is not S or a conservative amino acid substitution thereof or E;
• or
• (v) comprising an amino acid sequence that is at least 90% identical to a fragment of residues 22 to 404 of wild-type RAGE as set forth in SEQ ID NO:
• 14, wherein the peptide comprises at least both residues 379 and 391 and wherein if residue 376 is present it is not W,
• wherein the residue at 379 is not Q or a conservative amino acid substitution thereof, or
• wherein the residue at 391 is not S or a conservative amino acid substitution thereof.