Conjugation of spermine enhances cellular uptake of the stapled peptide-based inhibitors of p53-Mdm2 interaction

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7412-5. doi: 10.1016/j.bmcl.2011.10.009. Epub 2011 Oct 12.

Abstract

We report the first synthesis of the C-terminally spermine-conjugated stapled peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological, biophysical and cellular uptake assays with the spermine-conjugated stapled peptides revealed that spermine conjugation minimally affects biological activity while significantly increases peptide helicity and cellular uptake without apparent cytotoxicity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Survival / drug effects
  • Cells / drug effects
  • Circular Dichroism
  • Fluorescein / chemistry
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Spermine / chemistry*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Peptides
  • Tumor Suppressor Protein p53
  • Spermine
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Fluorescein