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

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Title
Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1
Author(s)
R N Murugan; J E Park; D Lim; M Ahn; C Cheong; Taeho Kwon; K Y Nam; S H Choi; Bo Yeon Kim; D Y Yoon; M B Yaffe; Dae Yeul Yu; K S Lee; J K Bang
Bibliographic Citation
Bioorganic & Medicinal Chemistry, vol. 21, no. 9, pp. 2623-2634
Publication Year
2013
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.
Keyword
Cyclic peptomersKinase inhibitorsPolo-box domain (PBD)Solid phase peptide synthesis
ISSN
0968-0896
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmc.2013.02.020
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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