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Peptoid–Peptide Hybrid Ligands Targeting the Polo Box Domain of Polo‐Like Kinase 1
Author(s) -
Liu Fa,
Park JungEun,
Qian WenJian,
Lim Dan,
Scharow Andrej,
Berg Thorsten,
Yaffe Michael B.,
Lee Kyung S.,
Burke Terrence R.
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200206
Subject(s) - peptoid , pentapeptide repeat , plk1 , chemistry , peptide , residue (chemistry) , polo like kinase , stereochemistry , combinatorial chemistry , side chain , biochemistry , organic chemistry , cell cycle , cell , polymer
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.