Use of a retroinverso p53 peptide as an inhibitor of MDM2

J Am Chem Soc. 2004 Dec 22;126(50):16288-9. doi: 10.1021/ja044883w.

Abstract

An N-terminal helical region of the tumor suppressor p53 binds in a hydrophobic cleft of the oncoprotein MDM2. A retroinverso isomer of the natural N-terminal helical peptide was found to interact with MDM2 using the same hydrophobic residues, Phe, Trp, and Leu. We propose that the retroinverso d-peptide adopts a right-handed helical conformation to achieve functional mimicry of the p53 peptide.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Circular Dichroism
  • Enzyme-Linked Immunosorbent Assay
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / chemistry
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Protein Isoforms
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / pharmacology*

Substances

  • Nuclear Proteins
  • Peptide Fragments
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-mdm2