Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides.
J Lipid Res
; 48(9): 1915-23, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17570869
ABSTRACT
Recently, attention has been focused on pharmacological treatments that increase HDL cholesterol to prevent coronary artery disease. Despite three decades of extensive research of human apolipoprotein A-I (apoA-I), the major protein component of HDL, the molecular basis for its antiatherogenic and anti-inflammatory functions remain elusive. Another protein component of HDL, apoA-II, has structural features similar to those of apoA-I but does not possess atheroprotective properties. To understand the molecular basis for the effectiveness of apoA-I, we used model synthetic peptides. We designed analogs of the class A amphipathic helical motif in apoA-I that is responsible for solubilizing phospholipids. None of these analogs has sequence homology to apoA-I, but all are similar in their lipid-associating structural motifs. Although all of these peptide analogs interact with phospholipids to form peptidelipid complexes, the biological properties of these analogs are different. Physical-chemical and NMR studies of these peptides have enabled the delineation of structural requirements for atheroprotective and anti-inflammatory properties in these peptides. It has been shown that peptides that interact strongly with lipid acyl chains do not have antiatherogenic and anti-inflammatory properties. In contrast, peptides that associate close to the lipid head group (and hence do not interact strongly with the lipid acyl chain) are antiatherogenic and anti-inflammatory. Understanding the structure and function of apoA-I and HDL through studies of the amphipathic helix motif may lead to peptide-based therapies for inhibiting atherosclerosis and other related inflammatory lipid disorders.
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas A
/
Apolipoproteína A-I
/
Anti-Inflamatórios
/
Antioxidantes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos