Peptoid-Peptide hybrid ligands targeting the polo box domain of polo-like kinase 1

Chembiochem. 2012 Jun 18;13(9):1291-6. doi: 10.1002/cbic.201200206. Epub 2012 May 8.

Abstract

We replaced the amino terminal Pro residue of the Plk1 polo-box-domain-binding pentapeptide (PLHSpT) with a library of N-alkyl-Gly "peptoids", and identified long-chain tethered phenyl moieties giving greater than two-orders-of-magnitude affinity enhancement. Further simplification by replacing the peptoid residue with appropriate amides gave low-nanomolar affinity N-acylated tetrapeptides. Binding of the N-terminal long-chain phenyl extension was demonstrated by X-ray co-crystal data.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism*
  • Ligands
  • Models, Molecular
  • N-substituted Glycines / chemistry
  • N-substituted Glycines / metabolism
  • Peptoids / chemistry
  • Peptoids / metabolism*
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Ligands
  • N-substituted Glycines
  • Peptoids
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases