Patent ID: 7250407

Claim:
A nucleotide sequence encoding a multimeric ApoA-I agonist which exhibits at least about 38% LCAT activation activity as compared with human ApoA-I and which has the structural formula (IV): HH LL m −HH n LL m −HH (IV) Or a pharmaceutically acceptable salt thereof, wherein: each m is independently an integer from 0 to 1; Each “HH” is independently the ApoA-I agonist comprising: (i) a 15 to 29-residue peptide or peptide analogue which forms an amphipathic α-helix in the presence of lipids and which comprises the structural formula (I): X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -X 18 -X 19 -X 20 -X 21 -X 22 -X 23 or a pharmaceutically acceptable salt thereof, wherein: X 1 is Pro (P), Ala (A), Gly (G), Gln (Q), Asn (N) or Asp (D); X 2 is an aliphatic residue; X 3 is Leu (L) or Phe (F); X 4 is an acidic residue; X 5 is Leu (L) or Phe (F); X 6 is Leu (L) or Phe (F); X 7 is a hydrophilic residue; X 8 is an acidic or a basic residue; X 9 is Leu (L) or Gly (G); X 10 is Leu (L), Trp (W) or Gly (G); X 11 is a hydrophilic residue; X 12 is a hydrophilic residue; X 13 is Gly (G) or an aliphatic residue; X 14 is Len (L), Trp (W) or Gly (G); X 15 is a hydrophilic residue; X 16 is a hydrophobic residue; X 17 is a hydrophobic residue; X 18 is Gln (Q), Asn (N) or a basic residue; X 19 is Gln (Q), Asn (N) or a basic residue; X 20 is a basic residue; X 21 is an aliphatic residue; X 22 is a basic residue; X 23 is absent or a basic residue; or (ii) a deleted form of structural formula (I) in which at least one and up to eight of residues X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 , X 18 , X 19 , X 20 , X 21 and X 22 are deleted wherein said structural formula (I) forms an amphipathic α-helix in the presence of lipids; or (iii) an altered form of structural formula (I) in which at least one of residues X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 , X 18 , X 19 , X 20 , X 21 , X 22 or X 23 is conservatively substituted with another residue, Each “LL” is independently a bifunctional linker.