Generation of a cell-permeable cycloheptapeptidyl inhibitor against the peptidyl-prolyl isomerase Pin1

Org Biomol Chem. 2017 May 31;15(21):4540-4543. doi: 10.1039/c7ob00430c.

Abstract

Cyclic peptides are capable of binding and modulating challenging drug targets including protein-protein interactions. However, their lack of membrane permeability prevents their application against intracellular targets. In this study, we show that it is possible to design a cell-permeable and biologically active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl-prolyl isomerase Pin1 by integrating cell-penetrating and target-binding sequences.

MeSH terms

  • Cell Membrane Permeability*
  • Enzyme Inhibitors / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase / antagonists & inhibitors*
  • Peptides, Cyclic / metabolism*
  • Peptides, Cyclic / pharmacology*

Substances

  • Enzyme Inhibitors
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptides, Cyclic