Anti-inflammatory peptides grab on to the whiskers of atherogenic oxidized lipids.
The peptide 4F is known to have potent anti-atherogenic activity. 4F is an 18 residue peptide that has a sequence capable of forming a class A amphipathic helix. Several other class A amphipathic helical, 18 residue peptides with the same polar face but with increasing Phe residues on the nonpolar face have been synthesized with varying degrees of biological activity. In this work we compared the properties of the original 2F peptide, modeled on the consensus sequence of the amphipathic helical segments of the apolipoprotein A-I with the peptide 4F that has two Leu residues replaced with Phe. We demonstrate that the more biologically active 4F peptide has the greatest affinity for binding to several molecular species of oxidized lipids. Lipoprotein particles can be formed by solubilizing 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) with peptides. These solubilized lipoprotein particles extract oxidized lipid from liposomes of POPC containing 5 mol% of oxidized lipid. The peptides with the strongest anti-atherogenic activity interact most strongly with the oxidized lipid. The results show that there is a correlation between the biological potency of these peptides and their ability to interact with certain specific cytotoxic lipids, suggesting that this interaction may contribute favourably to their biological properties.
Epand
Raquel F
RF
Department of Biochemistry and Biomedical Sciences, McMaster University Health Science Center, Hamilton, Ontario, Canada L8N 3Z5. epand@mcmaster.ca
Mishra
Vinod K
VK
Palgunachari
Mayakonda N
MN
Anantharamaiah
G M
GM
Epand
Richard M
RM
D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D050197:Atherosclerosis / Q000517:prevention & control; D002152:Calorimetry, Differential Scanning; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000737:chemistry; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry
C543859:1-0-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocoline; C544326:1-palmitoyl-2-(4-ketododec-3-enedioyl)phosphatidylcholine; C544327:1-palmitoyl-2-(5-keto-6-octenedioyl)phosphatidylcholine; C400185:1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; D000893:Anti-Inflammatory Agents; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D010767:Phosphorylcholine