title: Peptoid-Peptide hybrid ligands targeting the polo box domain of polo-like kinase 1.
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.
authors.affiliation: Chemical Biology Laboratory, Frederick National Lab, NCI, NIH, Frederick, MD 21702, USA.
authors.forename: Fa
authors.initials: F
authors.lastname: Liu
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Qian
authors.forename: Dan
authors.initials: D
authors.lastname: Lim
authors.forename: Andrej
authors.initials: A
authors.lastname: Scharow
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berg
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D034442:N-substituted Glycines / Q000737:chemistry / Q000378:metabolism; D034444:Peptoids / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D008024:Ligands; D034442:N-substituted Glycines; D034444:Peptoids; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1