ArticleJournal of medicinal chemistry2011
Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
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- The Increasing Value of Biomass: Moving From C6 Carbohydrates to Multifunctionalized Building Blocks via 5-(hydroxymethyl)furfural.ChemistryOpen · 2020Review
- Synthesis of an α-phosphono-α,α-difluoroacetamide analogue of the diphosphoinositol pentakisphosphate 5-InsPMedChemComm · 2019Article
- High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design.Acta crystallographica. Section D, Structural biology · 2018Article
- X-ray Characterization and Structure-Based Optimization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors.Journal of medicinal chemistry · 2017Article
- Druggability analysis and classification of protein tyrosine phosphatase active sites.Drug design, development and therapy · 2016Article
- Structure of human dual-specificity phosphatase 7, a potential cancer drug target.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Synthetic derivatives of the SUMO consensus sequence provide a basis for improved substrate recognition.Bioorganic & medicinal chemistry letters · 2015Article
- Integrating virtual and biochemical screening for protein tyrosine phosphatase inhibitor discovery.Methods (San Diego, Calif.) · 2014Article
- Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase.Journal of medicinal chemistry · 2013Article
- Biomolecular Interactions of small-molecule inhibitors affecting the YopH protein tyrosine phosphatase.Chemical biology & drug design · 2013Article
- Structure-guided studies of the SHP-1/JAK1 interaction provide new insights into phosphatase catalytic domain substrate recognition.Journal of structural biology · 2013Article
- Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.Bioorganic & medicinal chemistry letters · 2013Article
- Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a potential therapeutic target for Chagas' disease.Molecular and biochemical parasitology · 2013Article
- Small molecule tools for functional interrogation of protein tyrosine phosphatases.The FEBS journal · 2013Review
- Oxime-based linker libraries as a general approach for the rapid generation and screening of multidentate inhibitors.Nature protocols · 2012Article
- Oxime-based click chemistry in the development of 3-isoxazolecarboxylic acid containing inhibitors of Yersinia pestis protein tyrosine phosphatase, YopH.ChemMedChem · 2011Article
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7 authors at 4 institutions in 1 country.
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Abstract
Our current study reports the first K(M) optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K(M) = 80 μM) was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC(50) = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.
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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.