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

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.

• Authors: G M Anantharamaiah, Vinod K Mishra, David W Garber, Geeta Datta, Shaila P Handattu, Mayakonda N Palgunachari, Manjula Chaddha, Mohamad Navab, Srinivasa T Reddy, Jere P Segrest, Alan M Fogelman
• Journal: Journal of lipid research (J Lipid Res) Vol. 48 Issue 9 Pg. 1915-23 (Sep 2007) ISSN: 0022-2275 [Print] United States
• PMID: 17570869 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Apolipoprotein A-I
• Apolipoproteins A
• Cholesterol, HDL

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antioxidants (therapeutic use)
• Apolipoprotein A-I (chemistry, therapeutic use)
• Apolipoproteins A (therapeutic use)
• Atherosclerosis (drug therapy)
• Biomimetic Materials (therapeutic use)
• Cholesterol, HDL (physiology)
• Humans
• Models, Molecular
• Protein Structure, Secondary
• Structure-Activity Relationship