Abstract
An important goal in the development of polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors is selectivity for Plk1 relative to Plk2 and Plk3. In our current work we show that Plk1 PBD selectivity can be significantly enhanced by modulating interactions within a previously discovered "cryptic pocket" and a more recently identified proximal "auxiliary pocket."
Keywords:
Cryptic binding pocket; Plk1; Polo-box domain; Selectivity.
Published by Elsevier Ltd.
MeSH terms
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / metabolism
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Humans
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Molecular Docking Simulation
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Peptides / chemistry*
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Peptides / pharmacology*
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Polo-Like Kinase 1
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / metabolism
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Structure-Activity Relationship
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Tumor Suppressor Proteins
Substances
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Cell Cycle Proteins
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Peptides
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Tumor Suppressor Proteins
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PLK3 protein, human
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PLK2 protein, human
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Protein Serine-Threonine Kinases