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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.

SUBMITTER: Murugan RN 

PROVIDER: S-EPMC7561269 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1.

Murugan Ravichandran N RN   Park Jung-Eun JE   Lim Dan D   Ahn Mija M   Cheong Chaejoon C   Kwon Taeho T   Nam Ky-Youb KY   Choi Sun Ho SH   Kim Bo Yeon BY   Yoon Do-Young DY   Yaffe Michael B MB   Yu Dae-Yeul DY   Lee Kyung S KS   Bang Jeong Kyu JK  

Bioorganic & medicinal chemistry 20130227 9


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 combinati  ...[more]

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