Discovery and binding studies on a series of novel Pin1 ligands

Chem Biol Drug Des. 2009 Apr;73(4):369-79. doi: 10.1111/j.1747-0285.2009.00795.x.

Abstract

Pin1 plays a key role in various biological cellular processes via the recognition of phosphorylated Ser/Thr-Proline motifs. Moreover, high expression levels of Pin1 are correlated to tumorgenesis in some cancer types. Here, we identify a novel series of small molecular weight compounds with a core structure mimicking the phoshorylated serine. The binding affinity and binding mode of the compounds for Pin1 are analyzed via NMR spectroscopy and computational studies. The reported chemical probes and relative binding data to Pin1 represent valuable stepping stones for the validation of Pin1 as target for drug discovery and for eventually the development of possible lead compounds.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Computer Simulation
  • Escherichia coli / genetics
  • Humans
  • Ligands
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptidylprolyl Isomerase / antagonists & inhibitors*
  • Peptidylprolyl Isomerase / chemistry
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Serine / chemistry
  • Serine / metabolism
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / metabolism*

Substances

  • Ligands
  • Small Molecule Libraries
  • Serine
  • Peptidylprolyl Isomerase