ArticleChemistry & biology2012
Synthesis of a phosphoserine mimetic prodrug with potent 14-3-3 protein inhibitory activity.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 59 citations in OpenAlex.
- Synthetic trap-peptides identify a TOM complex phosphatase - PP2A dephosphorylates Tom6.The FEBS journal · 2026Article
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.JACS Au · 2024Article
- PermaPhosbioRxiv : the preprint server for biology · 2021Article
- Conservation of Cdc14 phosphatase specificity in plant fungal pathogens: implications for antifungal development.Scientific reports · 2020Article
- Phosphonopeptides containing free phosphonic groups: recent advances.RSC advances · 2020Review
- Molecular Dynamics Investigations Suggest a Non-specific Recognition Strategy of 14-3-3σ Protein by Tweezer: Implication for the Inhibition Mechanism.Frontiers in chemistry · 2019Article
- Modulators of 14-3-3 Protein-Protein Interactions.Journal of medicinal chemistry · 2018Review
- Structure-Based Design of Non-natural Macrocyclic Peptides That Inhibit Protein-Protein Interactions.Journal of medicinal chemistry · 2017Article
- Chemical Proteomics for Target Discovery of Head-to-Tail Cyclized Mini-Proteins.Frontiers in chemistry · 2017Article
- Direct Activation of Bax Protein for Cancer Therapy.Medicinal research reviews · 2016Review
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- Article
- Efficient delivery of cell impermeable phosphopeptides by a cyclic peptide amphiphile containing tryptophan and arginine.Molecular pharmaceutics · 2013Article
- Unleashing a "true" pSer-mimic in the cell.Chemistry & biology · 2012Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
Many protein-protein interactions in cells are mediated by functional domains that recognize and bind to motifs containing phosphorylated serine and threonine residues. To create small molecules that inhibit such interactions, we developed methodology for the synthesis of a prodrug that generates a phosphoserine peptidomimetic in cells. For this study, we synthesized a small molecule inhibitor of 14-3-3 proteins that incorporates a nonhydrolyzable difluoromethylenephosphoserine prodrug moiety. The prodrug is cytotoxic at low micromolar concentrations when applied to cancer cells and induces caspase activation resulting in apoptosis. The prodrug reverses the 14-3-3-mediated inhibition of FOXO3a resulting from its phosphorylation by Akt1 in a concentration-dependent manner that correlates well with its ability to inhibit cell growth. This methodology can be applied to target a variety of proteins containing phosphoserine and other phosphoamino acid binding domains.
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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 Socratic graph.