Oral amphipathic peptides as therapeutic agents

Expert Opin Investig Drugs. 2006 Jan;15(1):13-21. doi: 10.1517/13543784.15.1.13.


Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma HDL-cholesterol levels. During systemic inflammation as occurs with atherosclerosis, Apolipoprotein A-I can be altered, reducing its ability to promote reverse cholesterol transport and HDL can become pro-inflammatory. Amphipathic peptides with either a class A amphipathic helix (D-4F) or a class G* amphipathic helix (D-[113-122]apoJ), or even those that are too small to form a helix (KRES and FREL) have some similar characteristics. Their interaction with lipids leads to a reduction in lipoprotein-lipid hydroperoxides that releases HDL-associated antioxidant enzymes, such as paraoxonase, therefore providing antiatherosclerosis and anti-inflammatory activity. In addition, the peptide D-4F stimulates the formation and cycling of pre-beta HDL. These amphipathic peptides appear to have therapeutic potential as oral agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • Apolipoprotein A-I / chemistry
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Cholesterol / immunology
  • Cholesterol / metabolism
  • Clusterin / chemistry
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endothelial Cells / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lipoproteins, HDL / immunology
  • Lipoproteins, HDL / metabolism
  • Molecular Mimicry
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / therapeutic use*
  • Protein Structure, Secondary


  • Anti-Inflammatory Agents
  • Apolipoprotein A-I
  • Clusterin
  • D-4F peptide
  • Lipoproteins, HDL
  • Peptides
  • Cholesterol