Design and synthesis of a cell-permeable, drug-like small molecule inhibitor targeting the polo-box domain of polo-like kinase 1.

ABSTRACT:

Background

Polo-like kinase-1 (Plk1) plays a crucial role in cell proliferation and the inhibition of Plk1 has been considered as a potential target for specific inhibitory drugs in anti-cancer therapy. Several research groups have identified peptide-based inhibitors that target the polo-box domain (PBD) of Plk1 and bind to the protein with high affinity in in vitro assays. However, inadequate proteolytic resistance and cell permeability of the peptides hinder the development of these peptide-based inhibitors into novel therapeutic compounds.

Methodology/principal findings

In order to overcome the shortcomings of peptide-based inhibitors, we designed and synthesized small molecule inhibitors. Among these molecules, bg-34 exhibited a high binding affinity for Plk1-PBD and it

SUBMITTER: Srinivasrao G 

PROVIDER: S-EPMC4161390 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature