Use of a retroinverso p53 peptide as an inhibitor of MDM2.
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.
Sakurai
Kaori
K
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Chung
Hak Suk
HS
Kahne
Daniel
D
D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*
D009687:Nuclear Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2