Peptides having reduced toxicity that stimulate cholesterol efflux

An isolated peptide of 100 amino acids or less in length having cholesterol efflux activity, the peptide comprising an amino acid sequence that is an amphipathic α-helix that has a non-polar surface and a polar surface, wherein the polar surface comprises charged and uncharged amino acid residues at the lipid-water interface, wherein the peptide comprises at least one of the following salt bridges:

• a salt bridge between positions 1 and 5, wherein position 1 is a positively charged residue and position 5 is an acidic residue;
• a salt bridge between positions 3 and 7, wherein position 3 is an acidic residue and position lis a positively charged residue,
• a salt bridge between positions 14 and 18, wherein position 14 is an acidic residue and position 18 is a positively charged residue, or
• a salt bridge between positions 19 and 23, wherein position 19 is a positively charged residue and position 23 is an acidic residue;
• and wherein the amino acid sequence has at least 60%, or at least 70%, 75%, 80%, 85%, or 90% identity to any one of the following amino acid sequences:
• (SEQ ID NO:
• 1)
• KVRSELEEWLAALRELAEELLARL,
• (SEQ ID NO:
• 2)
• EVESKLREWLAALRELAEELLARL,
• (SEQ ID NO:
• 3)
• EVRSKLEEWLAALEELARELLARL,
• (SEQ ID NO:
• 4)
• EVRSKLEEWLAALRELAERLLAEL,
• (SEQ ID NO:
• 5)
• KVESELREWLAALRELAEELLARL
• (SEQ ID NO:
• 6)
• KVRSELEEWLAALEELARELLARL
• (SEQ ID NO:
• 7)
• KVRSELEEWLAALRELAERLLAEL
• (SEQ ID NO:
• 8)
• EVESKLREWLAALEELARELLARL
• (SEQ ID NO:
• 9)
• EVESKLREWLAALRELAERLLAEL,
• or
• (SEQ ID NO:
• 10)
• EVRSKLEEWLAALEELARRLLAEL.

An isolated peptide of 100 amino acids or less in length having cholesterol efflux activity, the peptide comprising an amino acid sequence that is an amphipathic α-helix that has a non-polar surface and a polar surface, wherein the polar surface comprises charged and uncharged amino acid residues at the lipid-water interface, the peptide comprises:

• a positively charged residue at position 1 and an acidic residue at position 5, an acidic residue at position 3 and a positively charged residue at position 7, and an acidic residue at position 14 and a positively charged residue at position 18;
• a positively charged residue at position 1 and an acidic residue at position 5, an acidic residue at position 3 and an a positively charged residue at position 7, and a positively charged residue at position 19 and an acidic residue at position 23;
• a positively charged residue at position 1 and an acidic residue at position 5, an acidic residue at position 14 and a positively charged residue at position 18, and a positively charged residue at position 19 and an acidic residue at position 23;
• an acidic residue at position 3 and a positively charged residue at position 7, an acidic residue at position 14 and a positively charged residue at position 18, and a positively charged residue at position 19 and an acidic residue at position 23;
• and
• wherein the peptide comprises an amino acid sequence having at least 60% and the amino acid sequence has at least 60%, or at least 70%, 75%, 80%, 85%, or 90% identity to any one of the following amino acid sequences:
• (SEQ ID NO:
• 11)
• KVESELREWLAALEELARELLARL,
• (SEQ ID NO:
• 12)
• KVESELREWLAALRELAERLLAEL,
• (SEQ ID NO:
• 13)
• KVRSELEEWLAALEELARRLLAEL,
• or
• (SEQ ID NO:
• 14)
• EVESKLREWLAALEELARRLLAEL.

An isolated peptide of 100 amino acids or less in length having cholesterol efflux activity, the peptide comprising an amino acid sequence that is an amphipathic α-helix that has a non-polar surface and a polar surface, wherein the polar surface comprises charged and uncharged amino acid residues at the lipid-water interface, wherein the amino acid comprises an amino acid sequence X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21X22X23X24,

• and comprises at least one of the following salt bridges with reference to the amino acid sequence:
• position 24 and position 20, wherein position 24 is a positively charged residue and position 20 is an acidic residue;
• position 22 and position 18, wherein position 22 is an acidic residue and position 18 is a positively charged residue, position 11 and position 7, wherein position 11 is an acidic residue and position 7 is a positively charged residue, or position 6 and position 2, wherein position 6 is a positively charged residue and position 2 is an acidic residue;
• and
• a hydrophobic residue at each of positions 23, 19, 16, 15, 12, 9, 8, 5, 4, and 1.

An isolated peptide of 100 amino acids or less in length having cholesterol efflux activity, the peptide comprising an amino acid sequence that is an amphipathic α-helix that has a non-polar surface and a polar surface, wherein the polar surface comprises charged and uncharged amino acid residues at the lipid-water interface, wherein the peptide comprises at least one of the following salt bridges:

• a salt bridge between positions 24 and 20, wherein position 24 is a positively charged residue and position 20 is an acidic residue;
• a salt bridge between positions 22 and 18, wherein position 22 is an acidic residue and position 18 is a positively charged residue,
• a salt bridge between positions 11 and 7, wherein position 11 is an acidic residue and position 7 is a positively charged residue, or
• a salt bridge between positions 6 and 2, wherein position 6 is a positively charged residue and position 2 is an acidic residue;
• and wherein the amino acid sequence has at least 60%, or at least 70%, 75%, 80%, 85%, or 90% identity to any one of the following amino acid sequences:
• (SEQ ID NO:
• 16)
• LRALLEEALERLAALWEELESRVK,
• (SEQ ID NO:
• 17)
• LRALLEEALERLAALWERLKSEVE,
• (SEQ ID NO:
• 18)
• LRALLERALEELAALWEELKSRVE,
• (SEQ ID NO:
• 19)
• LEALLREALERLAALWEELKSRVE
• (SEQ ID NO:
• 20)
• LRALLEEALERLAALWERLESEVK
• (SEQ ID NO:
• 21)
• LRALLERALEELAALWEELESRVK
• (SEQ ID NO:
• 22)
• LEALLREALERLAALWEELESRVK
• (SEQ ID NO:
• 23)
• LRALLERALEELAALWERLKSEVE
• (SEQ ID NO:
• 24)
• LEALLREALERLAALWERLKSEVE,
• or
• (SEQ ID NO:
• 25)
• LEALLRRALEELAALWEELKSRVE.

An isolated peptide of 100 amino acids or less in length having cholesterol efflux activity, the peptide comprising an amino acid sequence that is an amphipathic α-helix that has a non-polar surface and a polar surface, wherein the polar surface comprises charged and uncharged amino acid residues at the lipid-water interface, the peptide comprises:

• a positively charged residue at position 24 and an acidic residue at position 20, an acidic residue at position 22 and a positively charged residue at position 18, and an acidic residue at position 11 and a positively charged residue at position 7;
• a positively charged residue at position 24 and an acidic residue at position 20, an acidic residue at position 22 and an a positively charged residue at position 18, and a positively charged residue at position 6 and an acidic residue at position 2;
• a positively charged residue at position 24 and an acidic residue at position 20, an acidic residue at position 11 and a positively charged residue at position 7, and a positively charged residue at position 6 and an acidic residue at position 2;
• an acidic residue at position 22 and a positively charged residue at position 18, an acidic residue at position 11 and a positively charged residue at position 7, and a positively charged residue at position 6 and an acidic residue at position 2;
• and
• wherein the peptide comprises an amino acid sequence having at least 60% and the amino acid sequence has at least 60%, or at least 70%, 75%, 80%, 85%, or 90% identity to any one of the following amino acid sequences:
• (SEQ ID NO:
• 26)
• LRALLERALEELAALWERLESEVK,
• (SEQ ID NO:
• 27)
• LEALLREALERLAALWERLESEVK,
• (SEQ ID NO:
• 28)
• LEALLRRALEELAALWEELESRVK,
• or
• (SEQ ID NO:
• 29)
• LEALLRRALEELAALWERLKSEVE.