Internalization and stability of a thymidylate synthase Peptide inhibitor in ovarian cancer cells

J Med Chem. 2014 Dec 26;57(24):10551-6. doi: 10.1021/jm501397h. Epub 2014 Dec 3.

Abstract

Information on the cellular internalization and stability of the ovarian cancer cell growth inhibitor peptide, LSCQLYQR (LR), is vital for lead optimization. Ad-hoc-synthesized LR/fluorescent-probe conjugates were used to monitor the internalization of the peptide. Mass spectrometry was used to identify adducts resulting from the thiol reactivity of the cysteine residue in LR. A mechanistic model is proposed to explain the observed change in intracellular peptide amount over time. Structural modifications can be foreseen to improve the peptide stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Fluorescence
  • Humans
  • Microscopy, Confocal
  • Molecular Structure
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / enzymology
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology*
  • Tandem Mass Spectrometry
  • Thymidylate Synthase / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Peptide Fragments
  • Thymidylate Synthase