title: Inhibitors of the Polo-Box Domain of Polo-Like Kinase 1.
abstract: Polo-like kinase 1 (Plk1), a key player in mitosis, is overexpressed in a wide range of tumor types and has been validated as a target for tumor therapy. In addition to its N-terminal kinase domain, Plk1 harbors a C-terminal protein-protein interaction domain, referred to as the polo-box domain (PBD). Because the PBD is unique to the five-member family of polo-like kinases, and its inhibition is sufficient to inhibit the enzyme, the Plk1 PBD is an attractive target for the inhibition of Plk1 function. Although peptide-based inhibitors are invaluable tools for elucidating the nature of the binding interface, small molecules are better suited for the induction of mitotic arrest and apoptosis in tumor cells by Plk1 inhibition. This review describes the considerable progress that has been made in developing small-molecule and peptide-based inhibitors of the Plk1 PBD.
authors.affiliation: Leipzig University, Institute of Organic Chemistry, Johannisallee 29, 04103, Leipzig, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Berg
authors.affiliation: Leipzig University, Institute of Organic Chemistry, Johannisallee 29, 04103, Leipzig, Germany. tberg@uni-leipzig.de.
authors.forename: Thorsten
authors.identifier: http://orcid.org/0000-0003-3109-7696
authors.initials: T
authors.lastname: Berg
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D054852:Small Molecule Libraries; D000097869:Polo-Like Kinase 1
keywords: inhibitors; peptides; protein kinase; protein-protein interactions; small molecules