Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides.

Academic Article

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 peptide:lipid 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.
  • Published In

    Keywords

  • Animals, Anti-Inflammatory Agents, Antioxidants, Apolipoprotein A-I, Apolipoproteins A, Atherosclerosis, Biomimetic Materials, Cholesterol, HDL, Humans, Models, Molecular, Protein Structure, Secondary, Structure-Activity Relationship
  • Digital Object Identifier (doi)

    Author List

  • Anantharamaiah GM; Mishra VK; Garber DW; Datta G; Handattu SP; Palgunachari MN; Chaddha M; Navab M; Reddy ST; Segrest JP
  • Start Page

  • 1915
  • End Page

  • 1923
  • Volume

  • 48
  • Issue

  • 9