Peptide inhibitors of human HMG-CoA reductase as potential hypocholesterolemia agents

Biochem Biophys Res Commun. 2015 Jan 2;456(1):104-9. doi: 10.1016/j.bbrc.2014.11.042. Epub 2014 Nov 21.

Abstract

Hypercholesterolemia may lead to obesity and cardiovascular diseases. To prevent hypercholesterolemia, many drugs have been developed while searching for better drugs to treat hypercholesterolemia has never been ended. Other than small molecule drugs, peptide drugs are gaining more visibilities in many therapeutic areas. In the present study, we employed phage-display techniques to screen peptide inhibitors against human HMG-CoA reductase. The results indicate that the tetrapeptide PMAS inhibits hHMGR effectively (IC50=68 μM), could be a lead compound to develop hypocholesterolemic agents.

Keywords: HMG-CoA reductase; Molecule docking; Phage display.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / chemistry*
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Drug Design
  • Dyslipidemias / drug therapy*
  • Enzyme Inhibitors / chemistry*
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry*
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Peptide Library
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / metabolism

Substances

  • Anticholesteremic Agents
  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Peptide Library
  • Recombinant Proteins