title: Apolipoprotein Mimetic Peptides as Modulators of Lipoprotein Function.
abstract: Apolipoprotein (apo)A-I and apoE are the two protein components that have been extensively investigated for their anti-atherogenic properties. Both apolipoproteins possess amphipathic helical structures, responsible for the solubilization of lipids. While apoA-I possesses class A amphipathic helical structures, apoE possesses a 59 residue long amphipathic helical domain linked to a four helix bundle containing the Arg-rich, 10 residue receptor binding domain. An 18 residue model peptide (18A) was designed to mimic the amphipathic helical domains of apoA-I. This and several analogs were able solubilize phospholipids and, when administered into animal models of atherosclerosis, were able to inhibit lesion formation without any effect on plasma cholesterol levels. These analogs were subsequently termed as apoA-I mimetic peptides. When this peptide (18A) was covalently linked to the Arg-rich receptor binding domain of apoE, the resulting peptide Ac-hE18A-NH2, in which hE refers to the 141-150 Arg-rich region of apoE, dramatically reduced plasma cholesterol in several dyslipidemic animal models, resulting in the reduction of lesion formation. This and several other analogs which were able to dramatically decrease plasma cholesterol, analogous to apoE, were termed as apoE mimetic peptides. These observations developed the field of apolipoprotein mimetic peptides which are involved in interacting with lipoproteins and modulating their function. The present review describes progress made in this field which have culminated in clinical trials in humans for both the apoA-I and apoE mimetic peptides.
authors: University of Alabama at Birmingham, Department of Medicine, Division of Gerontology, Geriatrics and Palliative Care, Zeigler Res. Bldg., Room 1022, 703 19th Street S, Birmingham, AL 35294, USA.
authors: G M
authors: GM
authors: Anantharamaiah
authors: David W
authors: DW
authors: Garber
authors: C Roger
authors: CR
authors: White
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry*; D001057:Apolipoproteins E / Q000737:chemistry*; D050197:Atherosclerosis / Q000378:metabolism*; D040761:Biomimetic Materials; D032701:Biomimetics; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D002784:Cholesterol