Peptoid-Peptide Hybrid Ligands Targeting the Polo Box Domain of Polo-Like Kinase 1

Chemical Biology Laboratory, Frederick National Lab, NCI, NIH, Frederick, MD 21702, USA.
ChemBioChem (Impact Factor: 3.09). 06/2012; 13(9):1291-6. DOI: 10.1002/cbic.201200206
Source: PubMed


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.

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