ArticleBiopolymers2014
Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high Plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in HeLa cells.
Article in Biopolymers, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Structural regulation of PLK1 activity: implications for cell cycle function and drug discovery.Cancer gene therapy · 2025Review
- Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural Optimization and Anticancer Activity of Polo-like Kinase 1 (Plk1) Polo-Box Domain (PBD) Inhibitors and Their Prodrugs.ACS pharmacology & translational science · 2023Article
- Novel Macrocyclic Peptidomimetics Targeting the Polo-Box Domain of Polo-Like Kinase 1.Journal of medicinal chemistry · 2022Article
- Design and synthesis of a new orthogonally protected glutamic acid analog and its use in the preparation of high affinity polo-like kinase 1 polo-box domain - binding peptide macrocycles.Organic & biomolecular chemistry · 2021Article
- Development of a Polo-like Kinase-1 Polo-Box Domain Inhibitor as a Tumor Growth Suppressor in Mice Models.Journal of medicinal chemistry · 2020Article
- Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1.Journal of medicinal chemistry · 2020Article
- Peptidomimetic Polo-Box-Targeted Inhibitors that Engage PLK1 in Tumor Cells and Are Selective against the PLK3 Tumor Suppressor.ChemMedChem · 2020Article
- Histidine N(τ)-cyclized macrocycles as a new genre of polo-like kinase 1 polo-box domain-binding inhibitors.Bioorganic & medicinal chemistry letters · 2018Article
- Enhancing polo-like kinase 1 selectivity of polo-box domain-binding peptides.Bioorganic & medicinal chemistry · 2017Article
- The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis.Cancers · 2017Review
- Several inhibitors of the Plk1 Polo-Box Domain turn out to be non-specific protein alkylators.Cell cycle (Georgetown, Tex.) · 2017Article
- Phosphatase-Stable Phosphoamino Acid Mimetics That Enhance Binding Affinities with the Polo-Box Domain of Polo-like Kinase 1.ChemMedChem · 2017Article
- Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents.F1000Research · 2017Review
- Identification of Polo-like kinase 1 interaction inhibitors using a novel cell-based assay.Scientific reports · 2016Article
- Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy.Trends in pharmacological sciences · 2015Review
- Neighbor-directed histidine N (τ)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles.Biopolymers · 2015Article
- Mitsunobu mischief: neighbor-directed histidine N(τ)-alkylation provides access to peptides containing selectively functionalized imidazolium heterocycles.Organic & biomolecular chemistry · 2015Article
- Selective blockade of cancer cell proliferation and anchorage-independent growth by Plk1 activity-dependent suicidal inhibition of its polo-box domain.Cell cycle (Georgetown, Tex.) · 2015Article
- Putting a bit into the polo-box domain of polo-like kinase 1.Journal of analytical science and technologyReview
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.