title: Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1.
abstract: The polo-box domain (PBD) of polo-like kinase 1 (Plk1) is essentially required for the function of Plk1 in cell proliferation. The availability of the phosphopeptide-binding pocket on PBD provides a unique opportunity to develop novel protein-protein interaction inhibitors. Recent identification of a minimal 5-residue-long phosphopeptide, PLHSpT, as a Plk1 PBD-specific ligand has led to the development of several peptide-based inhibitors, but none of them is cyclic peptide. Through the combination of single-peptoid mimics and thio-ether bridged cyclization, we successfully demonstrated for the first time two cyclic peptomers, PL-116 and PL-120, dramatically improved the binding affinity without losing mono-specificity against Plk1 PBD in comparison with the linear parental peptide, PLHSpT. These cyclic peptomers could serve as promising templates for future drug designs to inhibit Plk1 PBD.
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Chung-Buk 363-883, Cheongwon, Republic of Korea.
authors.forename: Ravichandran N
authors.initials: RN
authors.lastname: Murugan
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Dan
authors.initials: D
authors.lastname: Lim
authors.forename: Mija
authors.initials: M
authors.lastname: Ahn
authors.forename: Chaejoon
authors.initials: C
authors.lastname: Cheong
authors.forename: Taeho
authors.initials: T
authors.lastname: Kwon
authors.forename: Ky-Youb
authors.initials: KY
authors.lastname: Nam
authors.forename: Sun Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Bang
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D019151:Peptide Library; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1