Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1.
Basic Information
ID: ALA2380215
Journal: Bioorg Med Chem
Title: Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1.
Authors: Murugan RN, Park JE, Lim D, Ahn M, Cheong C, Kwon T, Nam KY, Choi SH, Kim BY, Yoon DY, Yaffe MB, Yu DY, Lee KS, Bang JK.
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.
CiteXplore: 23498919
DOI: 10.1016/j.bmc.2013.02.020
Patent ID: ┄